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These disorders substantially increase the risk of cardiovascular, renal, and other multi-organ complications and have become a major global public health burden. Mitochondria are central organelles that integrate energy metabolism with stress signaling. They participate in fatty acid \u03b2-oxidation, the tricarboxylic acid cycle, and oxidative phosphorylation, while also regulating reactive oxygen species generation, mitochondrial DNA-related inflammatory signaling, calcium homeostasis, and cell death. Under chronic metabolic stress, the mitochondrial quality control (MQC) system shifts from adaptive repair toward decompensation, characterized by impaired mitochondrial biogenesis, abnormal mitochondrial dynamics, defective mitophagy, disrupted proteostasis and mitochondrial unfolded protein response, increased oxidative stress, and impaired metabolic reprogramming. Natural small molecules possess structural diversity and multi-target, multi-pathway regulatory properties. They can modulate multiple MQC processes and improve mitochondrial function and metabolic phenotypes in preclinical models. Novel formulations, structural optimization, and mitochondria-targeted delivery can further improve their solubility, bioavailability, tissue exposure, and subcellular localization, thereby enhancing therapeutic efficacy and translational potential. This review systematically summarizes the mechanisms of MQC dysregulation in metabolic diseases, the evidence supporting natural small-molecule interventions, and strategies for formulation and delivery optimization. Future studies should strengthen causal validation of MQC, quantify intramitochondrial drug exposure, and incorporate clinically relevant endpoints to facilitate the translation of natural small-molecule MQC modulators.<\/jats:p>","DOI":"10.3390\/ph19091402","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Small Molecules Targeting Mitochondrial Quality Control for the Treatment of Metabolic Diseases: Mechanisms, Novel Formulations, and Translational Perspectives"],"prefix":"10.3390","volume":"19","author":[{"given":"Chongyan","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102400, China"},{"name":"School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Baotou Medical College, Baotou 014040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0757-8476","authenticated-orcid":false,"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-7187","authenticated-orcid":false,"given":"Qingsong","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/nutrit\/nuy023","article-title":"Impact of nutrient overload on metabolic homeostasis","volume":"76","author":"Qiu","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ecl.2021.05.013","article-title":"An update on the epidemiology of type 2 diabetes: A global perspective","volume":"50","author":"Tinajero","year":"2021","journal-title":"Endocrinol. Metab. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7570\/jomes23052","article-title":"Metabolic dysfunction-associated steatotic liver disease (masld): A state-of-the-art review","volume":"32","author":"Chan","year":"2023","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41573-024-01084-2","article-title":"Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (mash)","volume":"24","author":"Do","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sandireddy, R., Sakthivel, S., Gupta, P., Behari, J., Tripathi, M., and Singh, B.K. (2024). Systemic impacts of metabolic dysfunction-associated steatotic liver disease (masld) and metabolic dysfunction-associated steatohepatitis (mash) on heart, muscle, and kidney related diseases. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1433857"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41586-024-08165-7","article-title":"Adipose tissue retains an epigenetic memory of obesity after weight loss","volume":"636","author":"Hinte","year":"2024","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/10998004211044754","article-title":"Effects of lifestyle intervention on inflammatory markers and waist circumference in overweight\/obese adults with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials","volume":"24","author":"Rahimi","year":"2022","journal-title":"Biol. Res. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1016\/j.cell.2024.04.037","article-title":"Mitochondria at the crossroads of health and disease","volume":"187","author":"Suomalainen","year":"2024","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/s41556-024-01410-1","article-title":"Mitochondrial heterogeneity and adaptations to cellular needs","volume":"26","author":"Kajimura","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41586-023-06866-z","article-title":"A break in mitochondrial endosymbiosis as a basis for inflammatory diseases","volume":"626","author":"Murphy","year":"2024","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41556-025-01625-w","article-title":"Mitochondrial genetics, signalling and stress responses","volume":"27","author":"Liu","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"ref_12","first-page":"32","article-title":"Mitochondrial quality control in human health and disease","volume":"11","author":"Liu","year":"2024","journal-title":"Mil. Med. Res. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41580-024-00785-1","article-title":"Molecular mechanisms of mitochondrial dynamics","volume":"26","author":"Segawa","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tips.2022.10.003","article-title":"Mitochondrial quality control mechanisms as therapeutic targets in doxorubicin-induced cardiotoxicity","volume":"44","author":"Wu","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_15","first-page":"59","article-title":"Targeting mitochondrial quality control: New therapeutic strategies for major diseases","volume":"11","author":"Hong","year":"2024","journal-title":"Mil. Med. Res. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Veluthakal, R., Esparza, D., Hoolachan, J.M., Balakrishnan, R., Ahn, M., Oh, E., Jayasena, C.S., and Thurmond, D.C. (2024). Mitochondrial dysfunction, oxidative stress, and inter-organ miscommunications in t2d progression. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031504"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"153356","DOI":"10.1016\/j.bbrc.2026.153356","article-title":"Mitochondrial dysfunction in mash: Focusing on chronic inflammation and intercellular communication","volume":"804","author":"Luo","year":"2026","journal-title":"Biochem. Biophys. Res. Commun. Biochem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107054","DOI":"10.1016\/j.phrs.2023.107054","article-title":"Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatment of diabetes and its complications: An update since 2010","volume":"200","author":"Lin","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1039\/D1FO03752H","article-title":"Curcumin alleviates hepatic steatosis by improving mitochondrial function in postnatal overfed rats and fatty l02 cells through the sirt3 pathway","volume":"13","author":"Du","year":"2022","journal-title":"Food Funct."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109414","DOI":"10.1016\/j.jnutbio.2023.109414","article-title":"Quercetin ameliorates nonalcoholic fatty liver disease (nafld) via the promotion of ampk-mediated hepatic mitophagy","volume":"120","author":"Cao","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108888","DOI":"10.1016\/j.jnutbio.2021.108888","article-title":"Nobiletin mitigates hepatocytes death, liver inflammation, and fibrosis in a murine model of nash through modulating hepatic oxidative stress and mitochondrial dysfunction","volume":"100","author":"Li","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12698","DOI":"10.1111\/jpi.12698","article-title":"Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia-reperfusion injury by improving mitochondrial quality control: Role of sirt6","volume":"70","author":"Yu","year":"2021","journal-title":"J. Pineal Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1186\/s12951-023-02165-x","article-title":"Advanced application of nanotechnology in active constituents of traditional chinese medicines","volume":"21","author":"Qiu","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1021\/acs.chemrev.8b00504","article-title":"Structural simplification of natural products","volume":"119","author":"Wang","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107100","DOI":"10.1016\/j.phrs.2024.107100","article-title":"Novel nano-drug delivery system for natural products and their application","volume":"201","author":"Huang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1021\/acs.jmedchem.0c01671","article-title":"A novel triphenylphosphonium carrier to target mitochondria without uncoupling oxidative phosphorylation","volume":"64","author":"Kulkarni","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.devcel.2021.02.009","article-title":"Quality control of the mitochondrion","volume":"56","author":"Ng","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R170","DOI":"10.1016\/j.cub.2018.01.004","article-title":"Mitophagy and quality control mechanisms in mitochondrial maintenance","volume":"28","author":"Pickles","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhao, D., Yan, Z., Yu, Y., Zhang, Y., and Luan, Z. (2026). From mechanisms to therapies: Exploiting epigenetic and post-translational modifications of mitochondrial quality control in diabetic kidney disease. Front. Endocrinol., 17.","DOI":"10.3389\/fendo.2026.1821507"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"560","DOI":"10.23876\/j.krcp.22.233","article-title":"Mitochondrial quality control and its emerging role in the pathogenesis of diabetic kidney disease","volume":"42","author":"Baek","year":"2023","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-024-01839-8","article-title":"Mitochondrial dysfunction: Mechanisms and advances in therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Tar."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4892","DOI":"10.1111\/jcmm.15194","article-title":"Mitochondrial biogenesis: An update","volume":"24","author":"Popov","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"Ampk: Guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14348\/molcells.2016.2318","article-title":"Sirt1 and the mitochondria","volume":"39","author":"Tang","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41392-023-01503-7","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Tar."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41392-024-01756-w","article-title":"Peroxisome proliferator-activated receptor gamma coactivator-1 (pgc-1) family in physiological and pathophysiological process and diseases","volume":"9","author":"Qian","year":"2024","journal-title":"Signal Transduct. Tar."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","article-title":"Nad(+) metabolism and its roles in cellular processes during ageing","volume":"22","author":"Covarrubias","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/1873-3468.12989","article-title":"The mitochondrial transcription factor tfam in neurodegeneration: Emerging evidence and mechanisms","volume":"592","author":"Kang","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"110000","DOI":"10.1016\/j.celrep.2021.110000","article-title":"The tfam-to-mtdna ratio defines inner-cellular nucleoid populations with distinct activity levels","volume":"37","author":"Jakobs","year":"2021","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41580-020-0210-7","article-title":"The cell biology of mitochondrial membrane dynamics","volume":"21","author":"Giacomello","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.cmet.2023.12.008","article-title":"Exercise induces tissue-specific adaptations to enhance cardiometabolic health","volume":"36","author":"Ashcroft","year":"2024","journal-title":"Cell Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","article-title":"Mitochondrial dynamics in health and disease: Mechanisms and potential targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.molcel.2023.02.012","article-title":"Determinants and outcomes of mitochondrial dynamics","volume":"83","author":"Scorrano","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.tcb.2020.09.008","article-title":"Mitochondrial fusion: The machineries in and out","volume":"31","author":"Gao","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102012","DOI":"10.1016\/j.jsps.2024.102012","article-title":"A detailed review of pharmacology of mfn1 (mitofusion-1)-mediated mitochondrial dynamics: Implications for cellular health and diseases","volume":"32","author":"Alghamdi","year":"2024","journal-title":"Saudi Pharm. J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zanfardino, P., Amati, A., Perrone, M., and Petruzzella, V. (2025). The balance of mfn2 and opa1 in mitochondrial dynamics, cellular homeostasis, and disease. Biomolecules, 15.","DOI":"10.20944\/preprints202502.1547.v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41586-018-0211-2","article-title":"Structural basis of mitochondrial receptor binding and constriction by drp1","volume":"558","author":"Kalia","year":"2018","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107531","DOI":"10.1016\/j.vph.2025.107531","article-title":"Balancing act: Drp1 inhibition and mitochondrial homeostasis in cardiovascular diseases","volume":"160","author":"Dubey","year":"2025","journal-title":"Vasc. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: Overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"EMBJ2020104705","DOI":"10.15252\/embj.2020104705","article-title":"Molecular mechanisms and physiological functions of mitophagy","volume":"40","author":"Onishi","year":"2021","journal-title":"Embo J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/s41556-024-01513-9","article-title":"The role of pink1\u2013parkin in mitochondrial quality control","volume":"26","author":"Narendra","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrm.2017.129","article-title":"Building and decoding ubiquitin chains for mitophagy","volume":"19","author":"Harper","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s10495-024-01977-y","article-title":"Mitophagy in health and disease. Molecular mechanisms, regulatory pathways, and therapeutic implications","volume":"29","year":"2024","journal-title":"Apoptosis Int. J. Program. Cell Death"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e202004029","DOI":"10.1083\/jcb.202004029","article-title":"Mitophagy pathways in health and disease","volume":"219","author":"Killackey","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1038\/s41467-018-05722-3","article-title":"Huwe1 e3 ligase promotes pink1\/parkin-independent mitophagy by regulating ambra1 activation via ikk\u03b1","volume":"9","author":"Peschiaroli","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/15548627.2019.1628520","article-title":"Phb2 (prohibitin 2) promotes pink1-prkn\/parkin-dependent mitophagy by the parl-pgam5-pink1 axis","volume":"16","author":"Yan","year":"2020","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cell.2016.11.042","article-title":"Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor","volume":"168","author":"Wei","year":"2017","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cmet.2017.12.008","article-title":"Basal mitophagy occurs independently of pink1 in mouse tissues of high metabolic demand","volume":"27","author":"McWilliams","year":"2018","journal-title":"Cell Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/1873-3468.14060","article-title":"Mitochondrial clearance: Mechanisms and roles in cellular fitness","volume":"595","author":"Onishi","year":"2021","journal-title":"FEBS Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.cell.2020.04.025","article-title":"Visualizing and modulating mitophagy for therapeutic studies of neurodegeneration","volume":"181","author":"Katayama","year":"2020","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41580-018-0092-0","article-title":"Mitochondrial proteins: From biogenesis to functional networks","volume":"20","author":"Pfanner","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrm.2017.110","article-title":"The mitochondrial upr: Mechanisms, physiological functions and implications in ageing","volume":"19","author":"Shpilka","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"M\u00fcnch, C. (2018). The different axes of the mammalian mitochondrial unfolded protein response. BMC Biol., 16.","DOI":"10.1186\/s12915-018-0548-x"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41418-019-0374-x","article-title":"Deletion of heat shock protein 60 in adult mouse cardiomyocytes perturbs mitochondrial protein homeostasis and causes heart failure","volume":"27","author":"Fan","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/s42255-025-01333-7","article-title":"Lonp1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes","volume":"7","author":"Li","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1016\/j.cub.2016.06.002","article-title":"The transcription factor atf5 mediates a mammalian mitochondrial upr","volume":"26","author":"Fiorese","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-biochem-052621-092014","article-title":"Replication and transcription of human mitochondrial dna","volume":"93","author":"Falkenberg","year":"2024","journal-title":"Annu. Rev. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11244","DOI":"10.1093\/nar\/gkaa804","article-title":"Mechanisms of replication and repair in mitochondrial dna deletion formation","volume":"48","author":"Fontana","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev-biochem-032620-104401","article-title":"Mitochondrial dna release in innate immune signaling","volume":"92","author":"Newman","year":"2023","journal-title":"Annu. Rev. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41423-023-01086-x","article-title":"Mitochondrial dna-triggered innate immune response: Mechanisms and diseases","volume":"20","author":"Hu","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41586-018-0372-z","article-title":"New mitochondrial dna synthesis enables nlrp3 inflammasome activation","volume":"560","author":"Zhong","year":"2018","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12196","DOI":"10.1073\/pnas.1708744114","article-title":"Dsba-l prevents obesity-induced inflammation and insulin resistance by suppressing the mtdna release-activated cgas-cgamp-sting pathway","volume":"114","author":"Bai","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"eaan5835","DOI":"10.1126\/science.aan5835","article-title":"Here, there, and everywhere: The importance of er membrane contact sites","volume":"361","author":"Wu","year":"2018","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41419-018-0416-1","article-title":"The role of endoplasmic reticulum-mitochondria contact sites in the control of glucose homeostasis: An update","volume":"9","author":"Rieusset","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.cmet.2018.03.003","article-title":"Mitochondria bound to lipid droplets have unique bioenergetics, composition, and dynamics that support lipid droplet expansion","volume":"27","author":"Benador","year":"2018","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nature25486","article-title":"Mitochondria\u2013lysosome contacts regulate mitochondrial fission via rab7 gtp hydrolysis","volume":"554","author":"Wong","year":"2018","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s42255-024-00978-0","article-title":"Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to rala activation","volume":"6","author":"Xia","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s42255-018-0021-8","article-title":"Metabolic adaptation and maladaptation in adipose tissue","volume":"1","author":"Chouchani","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2018.11.002","article-title":"New advances in adaptive thermogenesis: Ucp1 and beyond","volume":"29","author":"Chouchani","year":"2019","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41591-020-1126-7","article-title":"Brown adipose tissue is associated with cardiometabolic health","volume":"27","author":"Becher","year":"2021","journal-title":"Nat. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"C461","DOI":"10.1152\/ajpcell.00388.2021","article-title":"The importance of mitochondrial quality control for maintaining skeletal muscle function across health span","volume":"322","author":"Sligar","year":"2022","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3892\/mmr.2025.13773","article-title":"Influence and treatment of insulin receptor substrate\/pi3k\/akt-mediated insulin resistance in diabetes mellitus (review)","volume":"33","author":"Tang","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1152\/physrev.00038.2012","article-title":"Exercise, glut4, and skeletal muscle glucose uptake","volume":"93","author":"Richter","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/s41467-019-10189-x","article-title":"Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic \u03b2-cells","volume":"10","author":"Haythorne","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/s41419-025-07936-y","article-title":"Mitochondrial quality control in diabetes mellitus and complications: Molecular mechanisms and therapeutic strategies","volume":"16","author":"Chen","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1042\/BCJ20230167","article-title":"Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing","volume":"480","author":"Rutter","year":"2023","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/j.celrep.2017.05.035","article-title":"Hepatic diacylglycerol-associated protein kinase c\u03b5 translocation links hepatic steatosis to hepatic insulin resistance in humans","volume":"19","author":"Gilijamse","year":"2017","journal-title":"Cell Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of nafld development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jhep.2022.09.020","article-title":"Mitochondrial alterations in fatty liver diseases","volume":"78","author":"Fromenty","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e13622","DOI":"10.1111\/eci.13622","article-title":"Mitochondria, oxidative stress and nonalcoholic fatty liver disease: A complex relationship","volume":"52","author":"Simoes","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1053\/j.gastro.2018.06.083","article-title":"Mitochondrial dysfunction and signaling in chronic liver diseases","volume":"155","author":"Mansouri","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"154708","DOI":"10.1016\/j.metabol.2021.154708","article-title":"Mitochondrial dynamics and nonalcoholic fatty liver disease (nafld): New perspectives for a fairy-tale ending?","volume":"117","author":"Longo","year":"2021","journal-title":"Metab. Clin. Exp."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1172\/JCI83885","article-title":"Hepatocyte mitochondrial dna drives nonalcoholic steatohepatitis by activation of tlr9","volume":"126","author":"Santoro","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1053\/j.gastro.2018.09.010","article-title":"Expression of sting is increased in liver tissues from patients with nafld and promotes macrophage-mediated hepatic inflammation and fibrosis in mice","volume":"155","author":"Luo","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.jhep.2017.01.022","article-title":"Nlrp3 inflammasome blockade reduces liver inflammation and fibrosis in experimental nash in mice","volume":"66","author":"Mridha","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nri.2017.11","article-title":"Liver macrophages in tissue homeostasis and disease","volume":"17","author":"Krenkel","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jhep.2020.07.041","article-title":"Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis","volume":"74","author":"Gaul","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2445780","DOI":"10.1080\/07853890.2024.2445780","article-title":"Research advances in the diagnosis and treatment of masld\/mash","volume":"57","author":"Wang","year":"2025","journal-title":"Ann. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Chen, Q., Ruan, D., Shi, J., Du, D., and Bian, C. (2023). The multifaceted roles of natural products in mitochondrial dysfunction. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1093038"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Su, Z., Guo, Y., Huang, X., Feng, B., Tang, L., Zheng, G., and Zhu, Y. (2021). Phytochemicals: Targeting mitophagy to treat metabolic disorders. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.686820"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"12017","DOI":"10.1073\/pnas.0705070104","article-title":"AMP-activated protein kinase (ampk) action in skeletal muscle via direct phosphorylation of pgc-1\u03b1","volume":"104","author":"Handschin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1139\/apnm-2020-0005","article-title":"Pgc-1\u03b1-mediated regulation of mitochondrial function and physiological implications","volume":"45","author":"Halling","year":"2020","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3177\/jnsv.69.259","article-title":"Luteolin ameliorates hepatic steatosis and enhances mitochondrial biogenesis via ampk\/pgc-1\u03b1 pathway in western diet-fed mice","volume":"69","author":"Wang","year":"2023","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/jcsm.12530","article-title":"Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of ampk pathway","volume":"11","author":"Nishida","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"116314","DOI":"10.1016\/j.biopha.2024.116314","article-title":"Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle serca-sln mediated by camkii\/ampk\/pgc1\u03b1 pathway and mitochondrial biogenesis in female and male z\u00fccker diabetic fatty rats","volume":"172","author":"Salagre","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"de Lux\u00e1n-Delgado, B., Potes, Y., Rubio-Gonz\u00e1lez, A., Solano, J.J., Boga, J.A., Antu\u00f1a, E., Cach\u00e1n-Vega, C., Bermejo-Millo, J.C., Men\u00e9ndez-Coto, N., and Garc\u00eda-Gonz\u00e1lez, C. (2024). Melatonin alleviates liver mitochondrial dysfunction in leptin-deficient mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168677"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18013","DOI":"10.1021\/acs.jafc.4c03677","article-title":"Fucoxanthin mitigates high-fat-induced lipid deposition and insulin resistance in skeletal muscle through inhibiting pkm1 activity","volume":"72","author":"Wu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.cmet.2011.10.002","article-title":"Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans","volume":"14","author":"Timmers","year":"2011","journal-title":"Cell Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9299","DOI":"10.1021\/acs.jafc.1c03420","article-title":"Ginsenoside f2 suppresses adipogenesis in 3t3-l1 cells and obesity in micevia the ampk pathway","volume":"69","author":"Zhou","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"9157","DOI":"10.1038\/s41598-024-59758-1","article-title":"Ginsenoside rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation","volume":"14","author":"Feng","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Kim, K., Nam, K.H., Yi, S.A., Park, J.W., Han, J., and Lee, J. (2020). Ginsenoside rg3 induces browning of 3t3-l1 adipocytes by activating ampk signaling. Nutrients, 12.","DOI":"10.3390\/nu12020427"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"120488","DOI":"10.1016\/j.lfs.2022.120488","article-title":"Tanshinone 1 prevents high fat diet-induced obesity through activation of brown adipocytes and induction of browning in white adipocytes","volume":"298","author":"Jung","year":"2022","journal-title":"Life Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.lfs.2007.08.043","article-title":"Tanshinone iia inhibits atherosclerotic plaque formation by down-regulating mmp-2 and mmp-9 expression in rabbits fed a high-fat diet","volume":"81","author":"Fang","year":"2007","journal-title":"Life Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"111557","DOI":"10.1016\/j.mce.2022.111557","article-title":"Tanshinone iia and its derivative activate thermogenesis in adipocytes and induce \u201cbeiging\u201d of white adipose tissue","volume":"544","author":"Ma","year":"2022","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E5896","DOI":"10.1073\/pnas.1801745115","article-title":"Chemoproteomics reveals baicalin activates hepatic cpt1 to ameliorate diet-induced obesity and hepatic steatosis","volume":"115","author":"Dai","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e11984","DOI":"10.1002\/advs.202411984","article-title":"Alnustone ameliorates metabolic dysfunction-associated steatotic liver disease by facilitating mitochondrial fatty acid \u03b2-oxidation via targeting calmodulin","volume":"12","author":"Hu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1111\/bph.14935","article-title":"Berberine protects against diabetic kidney disease via promoting pgc-1\u03b1-regulated mitochondrial energy homeostasis","volume":"177","author":"Qin","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"16809","DOI":"10.1038\/s41598-024-67867-0","article-title":"Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating drp1-mediated mitochondrial apoptosis pathways","volume":"14","author":"Jia","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1007\/s12010-025-05211-6","article-title":"Astragaloside iv relieves mitochondrial oxidative stress damage and dysfunction in diabetic mice endothelial progenitor cells by regulating the gsk-3\u03b2\/nrf2 axis","volume":"197","author":"Zou","year":"2025","journal-title":"Appl. Biochem. Biotech."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"110187","DOI":"10.1016\/j.jnutbio.2025.110187","article-title":"Coenzyme q10 ameliorates obesity by promoting white adipose tissue browning and preserving mitochondrial dynamics in ovariectomized rats fed a high-fat diet","volume":"149","author":"Pan","year":"2026","journal-title":"J. Nutr. Biochem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e07324","DOI":"10.1016\/j.heliyon.2021.e07324","article-title":"Quercetin enhances fatty acid \u03b2-oxidation by inducing lipophagy in aml12 hepatocytes","volume":"7","author":"Fukaya","year":"2021","journal-title":"Heliyon"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13039","DOI":"10.1021\/acs.jafc.3c09132","article-title":"Elevated pink1\/parkin-dependent mitophagy and boosted mitochondrial function mediate protection of hepg2 cells from excess palmitic acid by hesperetin","volume":"72","author":"Li","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Xu, Z., Wu, X., Ye, L., Li, Z., Zhao, J., Zhang, Z., and Sun, Y. (2026). Lycopene ameliorates metabolic dysfunction-associated steatotic liver disease via pink1\/parkin-mediated mitophagy activation and apoptosis attenuation. Antioxidants, 15.","DOI":"10.3390\/antiox15050648"},{"key":"ref_126","first-page":"158009","article-title":"Myricetin stabilizes pink1 to activate mitophagy and ameliorate metabolic dysfunction-associated steatotic liver disease","volume":"155","author":"Xu","year":"2026","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"115121","DOI":"10.1016\/j.intimp.2025.115121","article-title":"Kaempferol improves mitochondrial homeostasis via mitochondrial dynamics and mitophagy in diabetic kidney disease","volume":"162","author":"Xia","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Zhong, Y., Jin, R., Luo, R., Liu, J., Ren, L., Zhang, Y., Shan, Z., and Peng, X. (2023). Diosgenin targets camkk2 to alleviate type ii diabetic nephropathy through improving autophagy, mitophagy and mitochondrial dynamics. Nutrients, 15.","DOI":"10.3390\/nu15163554"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3892\/ijmm.2012.1049","article-title":"Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis","volume":"30","author":"Kuo","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s12967-018-1685-2","article-title":"Matrine attenuates endoplasmic reticulum stress and mitochondrion dysfunction in nonalcoholic fatty liver disease by regulating serca pathway","volume":"16","author":"Gao","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An overview of nrf2 signaling pathway and its role in inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.biopha.2017.03.003","article-title":"Berberine inhibits palmitate-induced nlrp3 inflammasome activation by triggering autophagy in macrophages: A new mechanism linking berberine to insulin resistance improvement","volume":"89","author":"Zhou","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_134","first-page":"2091","article-title":"Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the nrf2\/are signalling pathway","volume":"17","author":"Deng","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"a033944","DOI":"10.1101\/cshperspect.a033944","article-title":"Signaling and regulation of the mitochondrial unfolded protein response","volume":"11","author":"Naresh","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.tcb.2020.01.008","article-title":"Mechanisms linking mitochondrial dysfunction and proteostasis failure","volume":"30","author":"Lu","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/hep.28245","article-title":"Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice","volume":"63","author":"Gariani","year":"2016","journal-title":"Hepatology"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Xie, L., Wang, Q., Dai, S., Li, B., Zhang, Y., Sun, Z., and Gao, Y. (2026). Agnuside stabilizes the complex i assembly factor ndufaf6 to reinforce mitochondrial efficiency and thermogenic responsiveness. Adv. Sci., e16501.","DOI":"10.1002\/advs.202516501"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"105737","DOI":"10.1016\/j.bioorg.2022.105737","article-title":"Dihydroartemisinin alleviates steatosis and inflammation in nonalcoholic steatohepatitis by decreasing endoplasmic reticulum stress and oxidative stress","volume":"122","author":"Li","year":"2022","journal-title":"Bioorg. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.biopha.2017.11.010","article-title":"Dihydroartemisinin inhibits er stress-mediated mitochondrial pathway to attenuate hepatocyte lipoapoptosis via blocking the activation of the pi3k\/akt pathway","volume":"97","author":"Chen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Liu, C., Wang, P., Gu, R., Zhao, K., Gao, Y., Tang, B., Shi, M., and Li, Z. (2025). Nanodelivery of bioactive natural products: A targeted therapeutic breakthrough for atherosclerosis. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17091102"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"116702","DOI":"10.1016\/j.biopha.2024.116702","article-title":"Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases","volume":"175","author":"Meng","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"16071","DOI":"10.1038\/natrevmats.2016.71","article-title":"Designing hydrogels for controlled drug delivery","volume":"1","author":"Li","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"10043","DOI":"10.1021\/acs.chemrev.7b00042","article-title":"Mitochondria-targeted triphenylphosphonium-based compounds: Syntheses, mechanisms of action, and therapeutic and diagnostic applications","volume":"117","author":"Zielonka","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1021\/acs.molpharmaceut.5c01400","article-title":"Curcumin-loaded liposomes (hplipo\/cur) with liver-targeting properties for efficient nafld treatment by alleviating mitochondrial ros-mediated ferroptosis via nrf2 pathway","volume":"23","author":"Wang","year":"2026","journal-title":"Mol. Pharm."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jconrel.2019.06.023","article-title":"The hepatic-targeted, resveratrol loaded nanoparticles for relief of high fat diet-induced nonalcoholic fatty liver disease","volume":"307","author":"Teng","year":"2019","journal-title":"J. Control Release"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"14911","DOI":"10.2147\/IJN.S557902","article-title":"Hepatocyte-targeted epicatechin nanoparticles promote autophagy and enhance mitochondrial function in metabolic dysfunction-associated steatotic liver disease","volume":"20","author":"Han","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e05925","DOI":"10.1002\/adhm.202505925","article-title":"Mitochondria-targeted liposomes boost thermogenesis for adipose tissue regulation","volume":"15","author":"Tian","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Khan, T., Waseem, R., Zehra, Z., Aiman, A., Bhardwaj, P., Ansari, J., Hassan, M.I., and Islam, A. (2022). Mitochondrial dysfunction: Pathophysiology and mitochondria-targeted drug delivery approaches. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122657"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1039\/D2FO04036K","article-title":"Hepatic parenchymal cell and mitochondrial-targeted astaxanthin nanocarriers for relief of high fat diet-induced nonalcoholic fatty liver disease","volume":"14","author":"Che","year":"2023","journal-title":"Food Funct."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1039\/D0RA09589C","article-title":"Mitochondria-targeted curcumin loaded ctpp\u2013peg\u2013pcl self-assembled micelles for improving liver fibrosis therapy","volume":"11","author":"Zhang","year":"2021","journal-title":"RSC Adv."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"115195","DOI":"10.1016\/j.addr.2024.115195","article-title":"Unlocking the mitochondria for nanomedicine-based treatments: Overcoming biological barriers, improving designs, and selecting verification techniques","volume":"207","author":"Pegoraro","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1021\/acs.bioconjchem.8b00732","article-title":"The endosomal escape of nanoparticles: Toward more efficient cellular delivery","volume":"30","author":"Smith","year":"2019","journal-title":"Bioconjugate Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"14708","DOI":"10.1074\/jbc.M611463200","article-title":"Interaction of the mitochondria-targeted antioxidant mitoq with phospholipid bilayers and ubiquinone oxidoreductases","volume":"282","author":"James","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.freeradbiomed.2011.11.026","article-title":"The mitochondria-targeted antioxidant mitoq decreases features of the metabolic syndrome in atm+\/\u2212\/apoe\u2212\/\u2212 mice","volume":"52","author":"Mercer","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"eadq4461","DOI":"10.1126\/sciadv.adq4461","article-title":"Reducing the mitochondrial oxidative burden alleviates lipid-induced muscle insulin resistance in humans","volume":"10","author":"Fiorenza","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1021\/acs.jmedchem.7b00741","article-title":"Development of a mitochondriotropic antioxidant based on caffeic acid: Proof of concept on cellular and mitochondrial oxidative stress models","volume":"60","author":"Teixeira","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.freeradbiomed.2021.12.304","article-title":"Mitochondriotropic antioxidant based on caffeic acid antioxcin(4) activates nrf2-dependent antioxidant defenses and quality control mechanisms to antagonize oxidative stress-induced cell damage","volume":"179","author":"Amorim","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"102400","DOI":"10.1016\/j.redox.2022.102400","article-title":"Mitochondria-targeted anti-oxidant antioxcin4 improved liver steatosis in western diet-fed mice by preventing lipid accumulation due to upregulation of fatty acid oxidation, quality control mechanism and antioxidant defense systems","volume":"55","author":"Amorim","year":"2022","journal-title":"Redox Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"24108","DOI":"10.1038\/srep24108","article-title":"Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by ampk-mediated nitric oxide and sirt3 regulation in endothelial cells: Potential implications in atherosclerosis","volume":"6","author":"Karnewar","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"111070","DOI":"10.1016\/j.intimp.2023.111070","article-title":"Therapeutic efficacy of mitochondria-targeted esculetin in the improvement of nafld-nash via modulating ampk-sirt1 axis","volume":"124","author":"Singuru","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00109-024-02449-1","article-title":"Mitochondria targeted esculetin administration improves insulin resistance and hyperglycemia-induced atherosclerosis in db\/db mice","volume":"102","author":"Singuru","year":"2024","journal-title":"J. Mol. Med."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Dvoretskaya, Y., Glanz, V., Gryaznova, M., Syromyatnikov, M., and Popov, V. (2021). Mitochondrial antioxidant skq1 has a beneficial effect in experimental diabetes as based on the analysis of expression of micrornas and mrnas for the oxidative metabolism regulators. Antioxidants, 10.","DOI":"10.3390\/antiox10111749"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6408278","DOI":"10.1155\/2017\/6408278","article-title":"Mitochondria-targeted antioxidant skq1 improves dermal wound healing in genetically diabetic mice","volume":"2017","author":"Demyanenko","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/ajcn\/nqy132","article-title":"A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: Safety, insulin-sensitivity, and lipid-mobilizing effects","volume":"108","author":"Dollerup","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1113\/JP278752","article-title":"Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men","volume":"598","author":"Dollerup","year":"2020","journal-title":"J. Physiol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s42255-019-0073-4","article-title":"The mitophagy activator urolithin a is safe and induces a molecular signature of improved mitochondrial and cellular health in humans","volume":"1","author":"Andreux","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"102322","DOI":"10.1016\/j.ctim.2020.102322","article-title":"Effects of curcuminoids on inflammatory status in patients with non-alcoholic fatty liver disease: A randomized controlled trial","volume":"49","author":"Keshvari","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1111\/dom.15070","article-title":"Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia","volume":"25","author":"Ciaraldi","year":"2023","journal-title":"Diabetes Obes. Metab."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"115274","DOI":"10.1016\/j.biopha.2023.115274","article-title":"Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies","volume":"165","author":"Luo","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mito.2020.12.010","article-title":"Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (nafld)","volume":"57","author":"Ajaz","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e00019","DOI":"10.1128\/MMBR.00072-19","article-title":"Bioavailability based on the gut microbiota: A new perspective","volume":"84","author":"Zhang","year":"2020","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1124\/dmd.119.086744","article-title":"Drug concentration asymmetry in tissues and plasma for small molecule-related therapeutic modalities","volume":"47","author":"Zhang","year":"2019","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"9420080","DOI":"10.26599\/FMH.2026.9420080","article-title":"Food and medicine homology components ameliorate metabolic diseases via dual pathways: Blood absorption and nonabsorptive pathways","volume":"2","author":"Zhai","year":"2026","journal-title":"Food Med. Homol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"9420058","DOI":"10.26599\/FMH.2025.9420058","article-title":"The improvement effect of ellagic acid and urolithins on metabolic diseases: Pharmacology and mechanism","volume":"3","author":"Wang","year":"2025","journal-title":"Food Med. Homol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41573-023-00774-7","article-title":"Artificial intelligence for natural product drug discovery","volume":"22","author":"Mullowney","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_178","first-page":"1","article-title":"TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches","volume":"19","author":"Wang","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1083\/jcb.201603039","article-title":"Mito-qc illuminates mitophagy and mitochondrial architecture in vivo","volume":"214","author":"McWilliams","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"7334","DOI":"10.1038\/s44318-025-00632-9","article-title":"Measuring mitochondrial membrane potential","volume":"44","author":"Rubio","year":"2025","journal-title":"EMBO J."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"7189","DOI":"10.1074\/jbc.M116.774471","article-title":"Quantifying intracellular rates of glycolytic and oxidative atp production and consumption using extracellular flux measurements","volume":"292","author":"Mookerjee","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_182","first-page":"e00311","article-title":"Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine","volume":"21","author":"Gropman","year":"2024","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:28:00Z","timestamp":1788841680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":182,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ph19091402"],"URL":"https:\/\/doi.org\/10.3390\/ph19091402","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}