{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:28:59Z","timestamp":1786969739762,"version":"build-2736575974"},"reference-count":122,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006054","name":"University of Guanajuato","doi-asserted-by":"publisher","award":["CIIC 048\/2025"],"award-info":[{"award-number":["CIIC 048\/2025"]}],"id":[{"id":"10.13039\/501100006054","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CIIC 048\/2025"],"award-info":[{"award-number":["CIIC 048\/2025"]}],"id":[{"id":"https:\/\/ror.org\/058cjye32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Obesity and type 2 diabetes (T2D) are multifactorial metabolic disorders characterized by progressive dysfunction of multiple organs and biological systems. Although mitochondrial dysfunction is a hallmark of disease progression, the mechanisms linking metabolic stress to coordinated tissue dysfunction remain incompletely understood. Comparative proteomic studies have consistently identified coordinated remodeling of oxidative phosphorylation, fatty acid oxidation, tricarboxylic acid cycle activity, redox regulation, mitochondrial proteostasis, and adaptive signaling across metabolically affected organs, revealing conserved organizational principles underlying mitochondrial adaptation. However, these findings have largely been interpreted within reductionist, pathway-centered frameworks. Here, we integrate evidence from comparative proteomics, mitochondrial biology, bioenergetics, redox biology, signaling, and systems biology to propose the concept of mitochondrial-centered biological networks (MCBNs), in which mitochondria function as dynamic regulatory hubs coordinating interconnected processes that collectively determine metabolic adaptation and tissue resilience. Building on this framework, we introduce the Mitochondrial Homeostasis Hypothesis, which proposes that preservation or restoration of mitochondrial homeostasis depends on coordinated regulation of MCBNs and constitutes a fundamental systems-level mechanism underlying resistance to obesity, T2D, and hypercaloric diet-induced metabolic dysfunction. Curcumin represents a well-studied network-modulating intervention that coordinately influences mitochondrial bioenergetics, metabolic flexibility, redox homeostasis, proteostasis, inflammatory signaling, and adaptive stress responses, supporting the concept that mitochondrial homeostasis is preserved through coordinated network regulation rather than isolated modulation of individual molecular pathways. Finally, we discuss how emerging technologies, including functional proteomics, redox proteomics, spatial and single-cell proteomics, acetylomics, integrated multi-omics, and artificial intelligence-assisted network analysis, provide unprecedented opportunities to quantitatively characterize MCBNs, validate the proposed hypothesis, identify network-based biomarkers, and accelerate the development of network-guided precision mitochondrial medicine.<\/jats:p>","DOI":"10.3390\/ijms27167334","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial-Centered Biological Networks in Metabolic Disease: Toward Precision Mitochondrial Medicine"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-9084","authenticated-orcid":false,"given":"Victoriano","family":"P\u00e9rez-V\u00e1zquez","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Guanajuato, Campus Le\u00f3n, Le\u00f3n 37320, Guanajuato, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4673-112X","authenticated-orcid":false,"given":"Juan Manuel","family":"Guzm\u00e1n-Flores","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Biociencias, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitl\u00e1n de Morelos 47620, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-5575","authenticated-orcid":false,"given":"Katya","family":"Vargas-Ortiz","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Guanajuato, Campus Le\u00f3n, Le\u00f3n 37320, Guanajuato, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Palacios-Reyes","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Guanajuato, Campus Le\u00f3n, Le\u00f3n 37320, Guanajuato, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-9120","authenticated-orcid":false,"given":"Joel","family":"Ram\u00edrez-Emiliano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Guanajuato, Campus Le\u00f3n, Le\u00f3n 37320, Guanajuato, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","unstructured":"WHO (2026, March 01). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_2","unstructured":"IDF (2026, March 01). IDF Diabetes Atlas 2025. Available online: https:\/\/diabetesatlas.org\/resources\/idf-diabetes-atlas-2025\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.immuni.2017.08.009","article-title":"Foundations of Immunometabolism and Implications for Metabolic Health and Disease","volume":"47","author":"Hotamisligil","year":"2017","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0140-6736(21)01919-X","article-title":"Obesity management as a primary treatment goal for type 2 diabetes: Time to reframe the conversation","volume":"399","author":"Lingvay","year":"2022","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: In Sickness and in Health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","article-title":"The multifaceted contributions of mitochondria to cellular metabolism","volume":"20","author":"Spinelli","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1126\/science.1104343","article-title":"Mitochondrial Dysfunction and Type 2 Diabetes","volume":"307","author":"Lowell","year":"2005","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI77812","article-title":"The pathogenesis of insulin resistance: Integrating signaling pathways and substrate flux","volume":"126","author":"Samuel","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: A network-based approach to human disease","volume":"12","author":"Gulbahce","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biocel.2008.06.010","article-title":"Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases","volume":"41","author":"Aggarwal","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Aggarwal, B.B., Surh, Y.-J., and Shishodia, S. (2007). Antioxidant and anti-inflammatory properties of curcumin. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer.","DOI":"10.1007\/978-0-387-46401-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/bph.13621","article-title":"Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases","volume":"174","author":"Kunnumakkara","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrg3356","article-title":"Next-generation proteomics: Towards an integrative view of proteome dynamics","volume":"14","author":"Altelaar","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/wsbm.144","article-title":"Systems biology and the future of medicine","volume":"3","author":"Loscalzo","year":"2011","journal-title":"WIREs Syst. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tomeh, M.A., Hadianamrei, R., and Zhao, X. (2019). A Review of Curcumin and Its Derivatives as Anticancer Agents. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051033"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zheng, J., Cheng, J., Zheng, S., Feng, Q., and Xiao, X. (2018). Curcumin, A Polyphenolic Curcuminoid with Its Protective Effects and Molecular Mechanisms in Diabetes and Diabetic Cardiomyopathy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00472"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2016.23","article-title":"Mitonuclear communication in homeostasis and stress","volume":"17","author":"Mottis","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"e104705","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_26","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1126\/science.aax3768","article-title":"Mitocellular communication: Shaping health and disease","volume":"366","author":"Mottis","year":"2019","journal-title":"Science"},{"key":"ref_27","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. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2014.01.011","article-title":"Mitohormesis","volume":"19","author":"Yun","year":"2014","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.freeradbiomed.2015.11.032","article-title":"Mitohormesis in exercise training","volume":"98","author":"Merry","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1126\/science.1069492","article-title":"Systems Biology: A Brief Overview","volume":"295","author":"Kitano","year":"2002","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1016\/j.cmet.2022.10.008","article-title":"Mitochondrial signal transduction","volume":"34","author":"Picard","year":"2022","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"vbae099","DOI":"10.1093\/bioadv\/vbae099","article-title":"Current and future directions in network biology","volume":"4","author":"Zitnik","year":"2024","journal-title":"Bioinform. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s42255-023-00783-1","article-title":"Multifaceted mitochondria: Moving mitochondrial science beyond function and dysfunction","volume":"5","author":"Monzel","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/omi.2024.0110","article-title":"A Quadruple Revolution: Deciphering Biological Complexity with Artificial Intelligence, Multiomics, Precision Medicine, and Planetary Health","volume":"28","author":"Cong","year":"2024","journal-title":"OMICS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/bfgp\/elae013","article-title":"A comprehensive review of machine learning techniques for multi-omics data integration: Challenges and applications in precision oncology","volume":"23","author":"Acharya","year":"2024","journal-title":"Brief. Funct. Genom."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative Stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_39","first-page":"1","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2008","journal-title":"Biochem. J."},{"key":"ref_40","first-page":"e47865","article-title":"Mitochondria orchestrate proteostatic and metabolic stress responses","volume":"20","author":"Ott","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41580-020-00300-2","article-title":"Quality control of the mitochondrial proteome","volume":"22","author":"Song","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","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. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/MOL.0b013e328328d0a4","article-title":"PGC-1\u03b1, SIRT1 and AMPK, an energy sensing network that controls energy expenditure","volume":"20","author":"Auwerx","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.molcel.2023.02.016","article-title":"Metabolic sensing and control in mitochondria","volume":"83","author":"Liu","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41580-024-00730-2","article-title":"Fundamentals of redox regulation in biology","volume":"25","author":"Sies","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41580-023-00650-7","article-title":"Mitochondrial proteome research: The road ahead","volume":"25","author":"Baker","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-omics approaches to disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrg.2018.4","article-title":"Integrative omics for health and disease","volume":"19","author":"Karczewski","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2174\/1570164613666160722102430","article-title":"Comparative Proteomics of Liver of the Diabetic Obese db\/db and Non-Obese or Diabetic Mice","volume":"13","year":"2016","journal-title":"Curr. Proteom."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Guzm\u00e1n-Flores, J., Flores-P\u00e9rez, E.C., Hern\u00e1ndez-Ortiz, M., Vargas-Ortiz, K., Ram\u00edrez-Emiliano, J., Encarnaci\u00f3n-Guevara, S., and P\u00e9rez-V\u00e1zquez, V. (2018). Protein Expression Profile of Twenty-Week-Old Diabetic db\/db and Non-Diabetic Mice Livers: A Proteomic and Bioinformatic Analysis. Biomolecules, 8.","DOI":"10.3390\/biom8020035"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Torres, A.K., Fleischhart, V., and Inestrosa, N.C. (2024). Mitochondrial unfolded protein response (UPR(mt)): What we know thus far. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1405393"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41589-024-01644-y","article-title":"The chemical language of protein glycation","volume":"21","author":"Martin","year":"2025","journal-title":"Nat. Chem. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12551-024-01188-4","article-title":"An overview on glycation: Molecular mechanisms, impact on proteins, pathogenesis, and inhibition","volume":"16","author":"Uceda","year":"2024","journal-title":"Biophys. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/s41392-023-01439-y","article-title":"Targeting protein modifications in metabolic diseases: Molecular mechanisms and targeted therapies","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"W415","DOI":"10.1093\/nar\/gkae456","article-title":"WebGestalt 2024: Faster gene set analysis and new support for metabolomics and multi-omics","volume":"52","author":"Elizarraras","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1080\/10286020.2013.802687","article-title":"Curcumin decreases oxidative stress in mitochondria isolated from liver and kidneys of high-fat diet-induced obese mice","volume":"15","year":"2013","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/0717-6287-47-74","article-title":"Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db\/db mice","volume":"47","year":"2014","journal-title":"Biol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8289","DOI":"10.3390\/molecules19068289","article-title":"A PPAR\u03b3, NF-\u03baB and AMPK-Dependent Mechanism May Be Involved in the Beneficial Effects of Curcumin in the Diabetic db\/db Mice Liver","volume":"19","year":"2014","journal-title":"Molecules"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9579","DOI":"10.3390\/ijms15069579","article-title":"Differential Proteomic Analysis of the Pancreas of Diabetic db\/db Mice Reveals the Proteins Involved in the Development of Complications of Diabetes Mellitus","volume":"15","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1139\/apnm-2013-0133","article-title":"Effects of curcumin on brain-derived neurotrophic factor levels and oxidative damage in obesity and diabetes","volume":"39","author":"Segovia","year":"2014","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.3390\/cimb46060345","article-title":"Multi Omics Applications in Biological Systems","volume":"46","author":"Onigbinde","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/EC-14-0092","article-title":"Mitochondrial dysfunction and insulin resistance: An update","volume":"4","author":"Montgomery","year":"2015","journal-title":"Endocr. Connect."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e70044","DOI":"10.1002\/edm2.70044","article-title":"Are Individuals with Type 2 Diabetes Metabolically Inflexible? A Systematic Review and Meta-Analysis","volume":"8","author":"Hansen","year":"2025","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1042\/CS20160897","article-title":"Redox theory of aging: Implications for health and disease","volume":"131","author":"Go","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kisty, E.A., Saart, E.C., and Weerapana, E. (2023). Identifying Redox-Sensitive Cysteine Residues in Mitochondria. Antioxidants, 12.","DOI":"10.3390\/antiox12050992"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e2200194","DOI":"10.1002\/pmic.202200194","article-title":"Thiol redox proteomics: Characterization of thiol-based post-translational modifications","volume":"23","author":"Li","year":"2023","journal-title":"Proteomics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"Pearce","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., De Leon-Oliva, D., Garc\u00eda-Montero, C., Fraile-Martinez, O., Boaru, D.L., de Castro, A.V., Saez, M.A., Lopez-Gonzalez, L., Bujan, J., and Alvarez-Mon, M.A. (2023). Reframing the link between metabolism and NLRP3 inflammasome: Therapeutic opportunities. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1232629"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-016-0303-y","article-title":"Mechanisms of inflammatory responses and development of insulin resistance: How are they interlinked?","volume":"23","author":"Rehman","year":"2016","journal-title":"J. Biomed. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Lee, Y.-M., and Kim, Y. (2024). Is Curcumin Intake Really Effective for Chronic Inflammatory Metabolic Disease? A Review of Meta-Analyses of Randomized Controlled Trials. Nutrients, 16.","DOI":"10.3390\/nu16111728"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41581-024-00889-z","article-title":"Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease","volume":"21","author":"Miguel","year":"2025","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-\u03b2: The master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.freeradbiomed.2024.06.001","article-title":"Metabolism and bioenergetics in the pathophysiology of organ fibrosis","volume":"222","author":"Miguel","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e20190103","DOI":"10.1084\/jem.20190103","article-title":"Transforming growth factor\u2013\u03b2 in tissue fibrosis","volume":"217","author":"Frangogiannis","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: From mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: The next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"716","DOI":"10.14336\/AD.2022.1101","article-title":"Pharmacological Mechanisms and Clinical Applications of Curcumin: Update","volume":"14","author":"Hao","year":"2023","journal-title":"Aging Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1021\/acsptsci.2c00012","article-title":"Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials","volume":"6","author":"Kunnumakkara","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Feige","year":"2009","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bbamcr.2010.09.019","article-title":"Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network","volume":"1813","author":"Scarpulla","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.bbrc.2009.08.018","article-title":"Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells","volume":"388","author":"Kim","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e28501","DOI":"10.1016\/j.heliyon.2024.e28501","article-title":"Curcumin simultaneously improves mitochondrial dynamics and myocardial cell bioenergy after sepsis via the SIRT1-DRP1\/PGC-1\u03b1 pathway","volume":"10","author":"Hou","year":"2024","journal-title":"Heliyon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPAR\u03b1 action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","article-title":"Integrated physiology and systems biology of PPAR\u03b1","volume":"3","author":"Kersten","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nm1025","article-title":"PPARs and the complex journey to obesity","volume":"10","author":"Evans","year":"2004","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"127042","DOI":"10.1016\/j.ijbiomac.2023.127042","article-title":"The global perspective on peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) in ectopic fat deposition: A review","volume":"253","author":"Qiu","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41574-023-00898-1","article-title":"Inter-organ crosstalk during development and progression of type 2 diabetes mellitus","volume":"20","author":"Xourafa","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of Nrf2 in Oxidative Stress and Toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12035-011-8181-5","article-title":"Modulation of Nrf2\/ARE Pathway by Food Polyphenols: A Nutritional Neuroprotective Strategy for Cognitive and Neurodegenerative Disorders","volume":"44","author":"Scapagnini","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yjmcc.2008.10.007","article-title":"Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes","volume":"46","author":"He","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/BST20150014","article-title":"Dissecting molecular cross-talk between Nrf2 and NF-\u03baB response pathways","volume":"43","author":"Wardyn","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1089\/ars.2015.6247","article-title":"The Redox Code","volume":"23","author":"Jones","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS Function in Redox Signaling and Oxidative Stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_100","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_101","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41589-024-01805-z","article-title":"Mechanisms of metabolism-coupled protein modifications","volume":"21","author":"Zhang","year":"2025","journal-title":"Nat. Chem. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1039\/D5CB00040H","article-title":"Cysteine sulfinic acid and sulfinylated peptides","volume":"6","author":"Hayward","year":"2025","journal-title":"RSC Chem. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1196\/annals.1333.014","article-title":"Dicarbonyl Intermediates in the Maillard Reaction","volume":"1043","author":"Thornalley","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"26512","DOI":"10.1074\/jbc.R113.464131","article-title":"The Redox Proteome","volume":"288","author":"Go","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","article-title":"Oxidative stress, inflammation, and cancer: How are they linked?","volume":"49","author":"Reuter","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41575-023-00832-w","article-title":"Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis","volume":"20","author":"Sharma","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature03354","article-title":"Nutrient control of glucose homeostasis through a complex of PGC-1\u03b1 and SIRT1","volume":"434","author":"Rodgers","year":"2005","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1210\/er.2002-0012","article-title":"Peroxisome Proliferator-Activated Receptor-\u03b3 Coactivator 1\u03b1 (PGC-1\u03b1): Transcriptional Coactivator and Metabolic Regulator","volume":"24","author":"Puigserver","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpa.2020.04.018","article-title":"Single-cell protein analysis by mass spectrometry","volume":"60","author":"Slavov","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1038\/s41592-024-02565-3","article-title":"Method of the Year 2024: Spatial proteomics","volume":"21","author":"Karimi","year":"2024","journal-title":"Nat. Methods"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41580-018-0094-y","article-title":"Spatial proteomics: A powerful discovery tool for cell biology","volume":"20","author":"Lundberg","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"103077","DOI":"10.1016\/j.copbio.2024.103077","article-title":"What\u2019s new in single-cell proteomics","volume":"86","author":"Truong","year":"2024","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e202400021","DOI":"10.1002\/pmic.202400021","article-title":"Review and Practical Guide for Getting Started with Single-Cell Proteomics","volume":"25","author":"Lin","year":"2025","journal-title":"Proteomics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev-biophys-021424-011450","article-title":"Single-Cell Proteomic Technologies: Tools in the Quest for Principles","volume":"55","author":"Slavov","year":"2026","journal-title":"Annu. Rev. Biophys."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nrm3841","article-title":"The growing landscape of lysine acetylation links metabolism and cell signalling","volume":"15","author":"Choudhary","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1042\/bse0520023","article-title":"Mitochondrial protein acetylation regulates metabolism","volume":"52","author":"Anderson","year":"2012","journal-title":"Essays Biochem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrg.2016.86","article-title":"Towards precision medicine","volume":"17","author":"Ashley","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/j.molcel.2022.05.022","article-title":"Unbiased spatial proteomics with single-cell resolution in tissues","volume":"82","author":"Mund","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrd4023","article-title":"Pharmacological approaches to restore mitochondrial function","volume":"12","author":"Andreux","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of Curcumin: Problems and Promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:11:56Z","timestamp":1786968716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":122,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167334"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167334","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]}}}