{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:47:31Z","timestamp":1782298051938,"version":"3.54.5"},"reference-count":112,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The second most prevalent neurodegenerative illness in the world, Parkinson\u2019s disease (PD), currently has no viable treatments. Although it is yet unknown if mitochondrial dysfunction is an initial event or evolves as a result of neurodegeneration, it is thought to be a crucial component of Parkinson\u2019s disease etiology. From the perspective of mitochondrial quality control (MQC), which includes PINK1\/Parkin-mediated mitophagy, mitochondrial dynamics, and mitochondrial proteostasis, this article examines mitochondrial dysfunction. Together, these processes preserve mitochondrial homeostasis and prevent the buildup of damaged mitochondria. Dysfunctional mitochondria gradually build up and cause oxidative stress and aberrant cellular signaling when mitochondrial quality control is compromised. According to available data, mitochondrial reactive oxygen species (mtROS) primarily worsen pre-existing mitochondrial damage by encouraging \u03b1-synuclein aggregation, cardiolipin remodeling, and dopamine oxidation. In addition, innate immune pathways like cGAS\u2013STING and TLR9 signaling can be triggered by mitochondrial damage-associated molecular patterns (mtDAMPs), especially mitochondrial DNA, which can lead to long-term neuroinflammatory reactions in PD. While new research suggests that m6A RNA modification may be involved in the regulation of mitochondrial stress, the PINK1\/Parkin pathway is crucial for maintaining mitochondrial homeostasis. Therapeutic approaches that target mitophagy augmentation, neuroinflammatory signaling, and mitochondrial protection have garnered increasing attention. In an attempt to improve mitochondrial function and lessen persistent neuroinflammatory activation, future research will probably need to concentrate on combination treatment techniques.<\/jats:p>","DOI":"10.3390\/cimb48070645","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:57:24Z","timestamp":1782287844000},"page":"645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Quality Control and Pathogenic Signaling Networks in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"48","author":[{"given":"Xiaobing","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengjing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-1939","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"},{"name":"Experiment Center for Medicial Science Research, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Public Health, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/538S1a","article-title":"Parkinson\u2019s disease","volume":"538","author":"Grayson","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/00207454.2011.620192","article-title":"Premotor symptoms and early diagnosis of Parkinson\u2019s disease","volume":"121","author":"Adler","year":"2011","journal-title":"Int. J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis of Parkinson\u2019s disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2021.08.009","article-title":"Dopamine in Parkinson\u2019s disease","volume":"522","author":"Latif","year":"2021","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104961","DOI":"10.1016\/j.neubiorev.2022.104961","article-title":"Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments","volume":"144","author":"Rehman","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yang, H.M. (2025). Mitochondrial Dysfunction in Neurodegenerative Diseases. Cells, 14.","DOI":"10.3390\/cells14040276"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100532","DOI":"10.1016\/j.cophys.2022.100532","article-title":"Mitochondria in neurodegeneration","volume":"26","author":"Chu","year":"2022","journal-title":"Curr. Opin. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00292","DOI":"10.1016\/j.neurot.2023.10.002","article-title":"Mitochondrial dysfunction in neurodegenerative disorders","volume":"21","author":"Klemmensen","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41583-023-00676-y","article-title":"Mitochondrial complex I deficiency and Parkinson disease","volume":"24","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3233\/JAD-240092","article-title":"Recent Advances of Mitochondrial Alterations in Alzheimer\u2019s Disease: A Perspective of Mitochondrial Basic Events","volume":"101","author":"Wei","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, X., Ma, Z., Lian, P., Xu, Y., and Cao, X. (2023). Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: A mini review. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1172197"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mito.2023.03.001","article-title":"A comprehensive perspective of Huntington\u2019s disease and mitochondrial dysfunction","volume":"70","author":"Dai","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mito.2023.05.007","article-title":"Mitochondrial dysfunction and oxidative stress in Alzheimer\u2019s disease, and Parkinson\u2019s disease, Huntington\u2019s disease and Amyotrophic Lateral Sclerosis\u2014An updated review","volume":"71","author":"Alqahtani","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.6823561","article-title":"Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis","volume":"219","author":"Langston","year":"1983","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1073\/pnas.82.7.2173","article-title":"Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity","volume":"82","author":"Javitch","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0140-6736(89)92366-0","article-title":"Mitochondrial complex I deficiency in Parkinson\u2019s disease","volume":"1","author":"Schapira","year":"1989","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ana.410260606","article-title":"Abnormalities of the electron transport chain in idiopathic Parkinson\u2019s disease","volume":"26","author":"Parker","year":"1989","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/jnc.13731","article-title":"Mitochondrial dysfunction in Parkinson\u2019s disease","volume":"139","author":"Bose","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1038\/s41467-024-47867-4","article-title":"Mitochondrial complex I deficiency stratifies idiopathic Parkinson\u2019s disease","volume":"15","author":"Toker","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","article-title":"Disruption of mitochondrial complex I induces progressive parkinsonism","volume":"599","author":"Zampese","year":"2021","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41392-022-00983-3","article-title":"Mitochondrial Complex I deficiency: Guilty in Parkinson\u2019s disease","volume":"7","author":"Vos","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, C., Turnbull, D.M., and Reeve, A.K. (2019). Mitochondrial Dysfunction in Parkinson\u2019s Disease-Cause or Consequence?. Biology, 8.","DOI":"10.3390\/biology8020038"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41593-021-00989-0","article-title":"Mitochondrial dysfunction and Parkinson\u2019s disease","volume":"25","author":"Wright","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-023-00676-7","article-title":"Mitochondrial dysfunction in Parkinson\u2019s disease\u2014A key disease hallmark with therapeutic potential","volume":"18","author":"Henrich","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nbd.2012.10.011","article-title":"Mitochondrial dysfunction and oxidative stress in Parkinson\u2019s disease and monogenic parkinsonism","volume":"51","author":"Hauser","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00204-017-2133-4","article-title":"An adverse outcome pathway for parkinsonian motor deficits associated with mitochondrial complex I inhibition","volume":"92","author":"Terron","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1523\/JNEUROSCI.0984-06.2006","article-title":"Parkinson\u2019s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled","volume":"26","author":"Keeney","year":"2006","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_29","first-page":"1356","article-title":"Mitochondrial Complex I as a Pathologic and Therapeutic Target for Parkinson\u2019s Disease","volume":"14","author":"Tryphena","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_30","first-page":"32","article-title":"Mitochondrial quality control in human health and disease","volume":"11","author":"Liu","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7128","DOI":"10.1111\/febs.15964","article-title":"Mitochondrial matrix proteases: Quality control and beyond","volume":"289","author":"Szczepanowska","year":"2022","journal-title":"FEBS J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jadiya, P., and Tomar, D. (2020). Mitochondrial Protein Quality Control Mechanisms. Genes, 11.","DOI":"10.3390\/genes11050563"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104553","DOI":"10.1016\/j.phrs.2019.104553","article-title":"Dynamin-related protein 1: A protein critical for mitochondrial fission, mitophagy, and neuronal death in Parkinson\u2019s disease","volume":"151","author":"Feng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_34","first-page":"551","article-title":"Dynamin-related protein 1 (Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury","volume":"32","author":"Wu","year":"2017","journal-title":"Histol. Histopathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s44318-025-00604-z","article-title":"A unified mechanism for mitochondrial damage sensing in PINK1-Parkin\u2013mediated mitophagy","volume":"45","author":"Thayer","year":"2026","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/s42003-024-06656-x","article-title":"Naturally occurring hyperactive variants of human parkin","volume":"7","author":"Huq","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Alonso-Navarro, H., Garc\u00eda-Mart\u00edn, E., and Ag\u00fandez, J.A.G. (2022). Coenzyme Q10 and Parkinsonian Syndromes: A Systematic Review. J. Pers. Med., 12.","DOI":"10.3390\/jpm12060975"},{"key":"ref_38","first-page":"3","article-title":"Mitochondrial electron transport chain, ROS generation and uncoupling (Review)","volume":"44","author":"Zhao","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102926","DOI":"10.1016\/j.redox.2023.102926","article-title":"Mitochondrial complex I ROS production and redox signaling in hypoxia","volume":"67","author":"Okoye","year":"2023","journal-title":"Redox Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41580-022-00456-z","article-title":"Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology","volume":"23","author":"Sies","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1089\/ars.2013.5280","article-title":"Cardiolipin and mitochondrial function in health and disease","volume":"20","author":"Paradies","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gammage, P.A., and Frezza, C. (2019). Mitochondrial DNA: The overlooked oncogenome?. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0668-y"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.molcel.2012.09.025","article-title":"Physiological roles of mitochondrial reactive oxygen species","volume":"48","author":"Sena","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104545","DOI":"10.1016\/j.nbd.2019.104545","article-title":"The role of dopamine in the pathogenesis of GBA1-linked Parkinson\u2019s disease","volume":"132","author":"Burbulla","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1126\/science.aam9080","article-title":"Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson\u2019s disease","volume":"357","author":"Burbulla","year":"2017","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Minakaki, G., Krainc, D., and Burbulla, L.F. (2020). The Convergence of Alpha-Synuclein, Mitochondrial, and Lysosomal Pathways in Vulnerability of Midbrain Dopaminergic Neurons in Parkinson\u2019s Disease. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.580634"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.molmed.2019.10.009","article-title":"Mitochondria-Lysosome Crosstalk: From Physiology to Neurodegeneration","volume":"26","author":"Deus","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/nn.3195","article-title":"Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury","volume":"15","author":"Ji","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/ncb2837","article-title":"Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells","volume":"15","author":"Chu","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41467-018-03241-9","article-title":"Cardiolipin exposure on the outer mitochondrial membrane modulates \u03b1-synuclein","volume":"9","author":"Ryan","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_53","first-page":"342ra78","article-title":"\u03b1-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson\u2019s disease","volume":"8","author":"Barrett","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chen, X.J., Coyne, L., Rana, A., Wang, X., Bhagwagar, S., Umino, Y., Solessio, E., and Middleton, F. (2025). Mitochondrial protein import stress augments \u03b1-synuclein aggregation and neural damage independent of bioenergetics. Res. Sq.","DOI":"10.21203\/rs.3.rs-3136613\/v1"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nri2975","article-title":"Mitochondria in innate immune responses","volume":"11","author":"West","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41577-024-01027-3","article-title":"DAMP sensing and sterile inflammation: Intracellular, intercellular and inter-organ pathways","volume":"24","author":"Huang","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eaao6047","DOI":"10.1126\/science.aao6047","article-title":"BAK\/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis","volume":"359","author":"McArthur","year":"2018","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"EMBR201949799","DOI":"10.15252\/embr.201949799","article-title":"Mitochondrial DNA in inflammation and immunity","volume":"21","author":"Riley","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2025.09.018","article-title":"VDAC1 oligomerization-mediated mtDNA release under sublethal oxidative stress: A novel inflammatory mechanism in vitiligo","volume":"241","author":"Gao","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s12276-023-00965-7","article-title":"Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway","volume":"55","author":"Kim","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nri.2017.21","article-title":"Mitochondrial DNA in innate immune responses and inflammatory pathology","volume":"17","author":"West","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"0012_4129","DOI":"10.4049\/jimmunol.212.supp.0012.4129","article-title":"Circulating oxidized mitochondrial DNA drives autoimmunity","volume":"212","author":"Xian","year":"2024","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.it.2023.01.006","article-title":"Oxidized mitochondrial DNA: A protective signal gone awry","volume":"44","author":"Xian","year":"2023","journal-title":"Trends Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s42003-023-04817-y","article-title":"Differential Binding of NLRP3 to non-oxidized and Ox-mtDNA mediates NLRP3 Inflammasome Activation","volume":"6","author":"Cabral","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1093\/hmg\/ddae031","article-title":"Mitochondrial DNA release and sensing in innate immune responses","volume":"33","author":"VanPortfliet","year":"2024","journal-title":"Hum. Mol. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eabe5085","DOI":"10.1126\/sciadv.abe5085","article-title":"Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome","volume":"7","author":"Kim","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/s41467-020-15119-w","article-title":"Microglia clear neuron-released \u03b1-synuclein via selective autophagy and prevent neurodegeneration","volume":"11","author":"Choi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1111\/cns.14157","article-title":"Microglial cGAS drives neuroinflammation in the MPTP mouse models of Parkinson\u2019s disease","volume":"29","author":"Ma","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab."},{"key":"ref_71","first-page":"1155","article-title":"Glycometabolic Reprogramming of Microglia in Neurodegenerative Diseases: Insights from Neuroinflammation","volume":"15","author":"Huang","year":"2024","journal-title":"Aging Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1007\/s10571-023-01376-y","article-title":"Microglial Metabolic Reprogramming: Emerging Insights and Therapeutic Strategies in Neurodegenerative Diseases","volume":"43","author":"Miao","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41593-021-00905-6","article-title":"Neuroinflammatory astrocyte subtypes in the mouse brain","volume":"24","author":"Hasel","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pajares, M., Rojo, A.I., Manda, G., Bosc\u00e1, L., and Cuadrado, A. (2020). Inflammation in Parkinson\u2019s Disease: Mechanisms and Therapeutic Implications. Cells, 9.","DOI":"10.3390\/cells9071687"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1089\/ars.2011.4019","article-title":"Mitochondrial quality control and dynamics in Parkinson\u2019s disease","volume":"16","author":"McCoy","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BST20150008","article-title":"The endoplasmic reticulum\/mitochondria interface: A subcellular platform for the orchestration of the functions of the PINK1-Parkin pathway?","volume":"43","author":"Erpapazoglou","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"O\u2019Callaghan, B., Hardy, J., and Plun-Favreau, H. (2023). PINK1: From Parkinson\u2019s disease to mitophagy and back again. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002196"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13024-019-0344-2","article-title":"LRRK2 Biology from structure to dysfunction: Research progresses, but the themes remain the same","volume":"14","author":"Berwick","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"120080","DOI":"10.1098\/rsob.120080","article-title":"PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65","volume":"2","author":"Kondapalli","year":"2012","journal-title":"Open Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nature13392","article-title":"Ubiquitin is phosphorylated by PINK1 to activate parkin","volume":"510","author":"Koyano","year":"2014","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1101\/gad.262758.115","article-title":"The three \u2018P\u2019s of mitophagy: PARKIN, PINK1, and post-translational modifications","volume":"29","author":"Durcan","year":"2015","journal-title":"Genes Dev."},{"key":"ref_83","first-page":"45","article-title":"Mitochondria and Parkinson\u2019s Disease: Clinical, Molecular, and Translational Aspects","volume":"11","author":"Borsche","year":"2021","journal-title":"J. Park. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neures.2020.01.006","article-title":"The PINK1\u2013Parkin axis: An Overview","volume":"159","author":"Tanaka","year":"2020","journal-title":"Neurosci. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"102720","DOI":"10.1016\/j.conb.2023.102720","article-title":"Novel insights into Parkin-mediated mitochondrial dysfunction and neuroinflammation in Parkinson\u2019s disease","volume":"80","author":"Pereira","year":"2023","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1111\/ejn.12872","article-title":"Evidence for a common biological pathway linking three Parkinson\u2019s disease-causing genes: Parkin, PINK1 and DJ-1","volume":"41","author":"Christoffels","year":"2015","journal-title":"Eur. J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1042\/BCJ20253062","article-title":"LRRK2-mediated mitochondrial dysfunction in Parkinson\u2019s disease","volume":"482","author":"Buck","year":"2025","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41531-024-00696-0","article-title":"Elevated \u03b1-synuclein levels inhibit mitophagic flux","volume":"10","author":"Kinnart","year":"2024","journal-title":"npj Park. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1523\/JNEUROSCI.0633-16.2016","article-title":"Compartmentalized Regulation of Parkin-Mediated Mitochondrial Quality Control in the Drosophila Nervous System In Vivo","volume":"36","author":"Sung","year":"2016","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13024-024-00701-3","article-title":"Mitochondrial CISD1\/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1\/parkin models","volume":"19","author":"Martinez","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1038\/s41401-021-00810-5","article-title":"PINK1 overexpression prevents forskolin-induced tau hyperphosphorylation and oxidative stress in a rat model of Alzheimer\u2019s disease","volume":"43","author":"Wang","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"151185","DOI":"10.1016\/j.ejcb.2021.151185","article-title":"Cannabidiol activates PINK1-Parkin-dependent mitophagy and mitochondrial-derived vesicles","volume":"101","author":"Ramirez","year":"2022","journal-title":"Eur. J. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41419-024-06439-6","article-title":"USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient human neurons","volume":"15","author":"Okarmus","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1021\/acschemneuro.8b00657","article-title":"Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death","volume":"10","author":"Chen","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"111303","DOI":"10.1016\/j.cellsig.2024.111303","article-title":"Mettl3-m6A-YTHDF1 axis promotion of mitochondrial dysfunction in metabolic dysfunction-associated steatotic liver disease","volume":"121","author":"Wang","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zhou, J., Han, Y., and Hou, R. (2023). Potential role of N6-methyladenosine modification in the development of Parkinson\u2019s disease. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1321995"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/hmg\/ddae029","article-title":"m6A RNA methylation regulates mitochondrial function","volume":"33","author":"Kahl","year":"2024","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhao, T., Yuan, C., and Chen, X. (2025). The Role of N6-Methyladenosine (m6A) RNA Modification in the Pathogenesis of Parkinson\u2019s Disease. Biomolecules, 15.","DOI":"10.3390\/biom15050617"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Duarte-Jurado, A.P., Gopar-Cuevas, Y., Saucedo-Cardenas, O., Loera-Arias, M.J., Montes-de-Oca-Luna, R., Garcia-Garcia, A., and Rodriguez-Rocha, H. (2021). Antioxidant Therapeutics in Parkinson\u2019s Disease: Current Challenges and Opportunities. Antioxidants, 10.","DOI":"10.3390\/antiox10030453"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Shinn, L.J., and Lagalwar, S. (2021). Treating Neurodegenerative Disease with Antioxidants: Efficacy of the Bioactive Phenol Resveratrol and Mitochondrial-Targeted MitoQ and SkQ. Antioxidants, 10.","DOI":"10.20944\/preprints202102.0573.v1"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.cmet.2022.02.001","article-title":"The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson\u2019s disease","volume":"34","author":"Brakedal","year":"2022","journal-title":"Cell Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/mdc3.13500","article-title":"Nicotinamide Adenine Dinucleotide Supplementation in Parkinson\u2019s Disease: A Potential Disease-Modifying Agent Targeting Multiple Pathways","volume":"9","author":"Rossi","year":"2022","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3390\/neuroglia5040026","article-title":"Harnessing Mitophagy for Therapeutic Advances in Aging and Chronic Neurodegenerative Diseases","volume":"5","author":"Ghosh","year":"2024","journal-title":"Neuroglia"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1017\/S0954422425100292","article-title":"Distinct roles of urolithin A and spermidine in mitophagy and autophagy: Implications for dietary supplementation","volume":"39","author":"Borsky","year":"2026","journal-title":"Nutr. Res. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI13505","article-title":"Role of AMP-activated protein kinase in mechanism of metformin action","volume":"108","author":"Zhou","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.neuron.2017.01.022","article-title":"Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities","volume":"93","author":"Menzies","year":"2017","journal-title":"Neuron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/emm.2016.16","article-title":"AMPK activators: Mechanisms of action and physiological activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Su, Q., Ng, W.L., Goh, S.Y., Gulam, M.Y., Wang, L.F., Tan, E.K., Ahn, M., and Chao, Y.X. (2022). Targeting the inflammasome in Parkinson\u2019s disease. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.957705"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41586-018-0287-8","article-title":"Targeting STING with covalent small-molecule inhibitors","volume":"559","author":"Haag","year":"2018","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS-STING pathway as a therapeutic target in inflammatory diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41531-022-00402-y","article-title":"Mitophagy and reactive oxygen species interplay in Parkinson\u2019s disease","volume":"8","author":"Xiao","year":"2022","journal-title":"npj Park. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Ahmed, S., Pasam, T., and Afreen, F. (2026). Mitophagy\u2013NLRP3 Inflammasome Crosstalk in Parkinson\u2019s Disease: Pathogenic Mechanisms and Emerging Therapeutic Strategies. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010486"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/645\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:04:30Z","timestamp":1782295470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":112,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070645"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070645","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}