AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Journal of Neurorestoratology Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review | Open Access

New perspectives on the role of mitochondria in Parkinson's disease

Shiyi Yin, Yongjiang Zhang, Jiannan Wu, Run Song, Mengmeng Shen, Xiaoyi Lai, Junqiang Yan( )
Neuromolecular Biology Laboratory, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan, China
Show Author Information

Abstract

Mitochondrial dysfunction is pivotal in the occurrence and development of Parkinson's disease (PD). Interventions to increase mitochondrial biogenesis and maintain the balance in mitochondrial turnover have the potential to protect against neurological damage. In addition to their crucial role in the tricarboxylic acid cycle, mitochondria impact diverse activities, including cellular metabolism, cellular quality control, and the production of reactive oxygen species. Thus, it has become imperative to better understand the regulation and function of mitochondria in PD. With this review, we aim to stimulate research that explores mitochondria-oriented neuroprotection strategies to maintain the balance in mitochondrial turnover. First, we summarize research on newly discovered genes that regulate PD mitochondrial autophagy through PTEN-induced kinase 1 (PINK1), namely AMBRA1, SYNJ2BP, and SIAH3. Second, we review PD-related mitochondrial proteins, including STRT3 and SIRT6, and the mitochondrial unfolded protein response, covering their mechanisms of involvement in PD. Third, we emphasize the roles of the mitochondrial complex, pyroptosis, and copper-induced cell death in mitochondrial damage in PD. Finally, we present a brief overview of new therapeutic strategies to correct mitochondrial defects that may be applicable for targeting mitochondria in PD patients.

Keywords

Oxidative stressMitophagyParkinson's diseaseMitochondrial dynamicsMitochondrial protein

References

1

Hayes MT. Parkinson's disease and Parkinsonism. Am J Med. 2019;132(7): 802–807. https://doi.org/10.1016/j.amjmed.2019.03.001.
Crossref Google Scholar
2

Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021;397(10291): 2284–2303. https://doi.org/10.1016/S0140-6736(21)00218-X.
Crossref Google Scholar
3

Asghar M, Odeh A, Fattahi AJ, et al. Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’ s disease and Lewy body dementia. Sci Rep. 2022;12(1):17578. https://doi.org/10.1038/s41598-022-22400-z.
Crossref Google Scholar
4

Kalia LV, Lang AE. Evolving basic, pathological and clinical concepts in PD. Nat Rev Neurol. 2016;12:65–66. https://doi.org/10.1038/nrneurol.2015.249.
Crossref Google Scholar
5

Domenighetti C, Sugier PE, Sreelatha AAK, et al. Mendelian randomisation study of smoking, alcohol, and coffee drinking in relation to Parkinson's dis-ease. J Parkinsons Dis. 2022;12(1):267–282. https://doi.org/10.3233/JPD-212851.
Crossref Google Scholar
6

Forbes JM, Thorburn DR. Mitochondrial dysfunction in diabetic kidney dis-ease. Nat Rev Nephrol. 2018;14(5):291–312. https://doi.org/10.1038/nrneph.2018.9.
Crossref Google Scholar
7

Toomey CE, Heywood WE, Evans JR, et al. Mitochondrial dysfunction is a key pathological driver of early stage Parkinson's. Acta Neuropathol Commun. 2022;10(1):134. https://doi.org/10.1186/s40478-022-01424-6.
Crossref Google Scholar
8

Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neuro-degenerative diseases. Nature. 2006;443(7113):787–795. https://doi.org/10.1038/nature05292.
Crossref Google Scholar
9

Srinivasan S, Guha M, Kashina A, et al. Mitochondrial dysfunction and mito-chondrial dynamics-The cancer connection. Biochim Biophys Acta Bioenerg. 2017;1858(8):602–614. https://doi.org/10.1016/j.bbabio.2017.01.004.
Crossref Google Scholar
10

Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol. 2020;15:235–259. https://doi.org/10.1146/annurev-pathmechdis-012419-032711.
Crossref Google Scholar
11

Yang YH, Karakhanova S, Hartwig W, et al. Mitochondria and mitochondrial ROS in cancer: novel targets for anticancer therapy. J Cell Physiol. 2016;231(12):2570–2581. https://doi.org/10.1002/jcp.25349.
Crossref Google Scholar
12

Yan YQ, Fang Y, Zheng R, et al. NLRP3 inflammasomes in Parkinson's disease and their regulation by parkin. Neuroscience. 2020;446:323–334. https://doi.org/10.1016/j.neuroscience.2020.08.004.
Crossref Google Scholar
13

Lin QS, Li S, Jiang N, et al. PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation. Redox Biol. 2019;26:101254. https://doi.org/10.1016/j.redox.2019.101254.
Crossref Google Scholar
14

Shahmoradian SH, Lewis AJ, Genoud C, et al. Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes. Nat Neurosci. 2019;22(7):1099–1109. https://doi.org/10.1038/s41593-019-0423-2.
Crossref Google Scholar
15

Lang AE, Espay AJ. Disease modification in Parkinson's disease: current ap-proaches, challenges, and future considerations. Mov Disord. 2018;33(5): 660–677. https://doi.org/10.1002/mds.27360.
Crossref Google Scholar
16

Szego EM, Malz L, Bernhardt N, et al. Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice. Elife. 2022;11:e81943. https://doi.org/10.7554/eLife.81943.
Crossref Google Scholar
17

Bertholet AM, Delerue T, Millet AM, et al. Mitochondrial fusion/fission dy-namics in neurodegeneration and neuronal plasticity. Neurobiol Dis. 2016;90: 3–19. https://doi.org/10.1016/j.nbd.2015.10.011.
Crossref Google Scholar
18

Vos M. Mitochondrial Complex Ⅰ deficiency: guilty in Parkinson's disease. Signal Transduct Targeted Ther. 2022;7(1):136. https://doi.org/10.1038/s41392-022-00983-3.
Crossref Google Scholar
19

Pradeepkiran JA, Reddy PH. Defective mitophagy in Alzheimer's disease. Ageing Res Rev. 2020;64:101191. https://doi.org/10.1016/j.arr.2020.101191.
Crossref Google Scholar
20

Gonzalez-Rodríguez P, Zampese E, Stout KA, et al. Disruption of mitochondrial complex Ⅰ induces progressive Parkinsonism. Nature. 2021;599(7886): 650–656. https://doi.org/10.1038/s41586-021-04059-0.
Crossref Google Scholar
21

O'Hanlon ME, Tweedy C, Scialo F, et al. Mitochondrial electron transport chain defects modify Parkinson's disease phenotypes in a Drosophila model. Neu-robiol Dis. 2022;171:105803. https://doi.org/10.1016/j.nbd.2022.105803.
Crossref Google Scholar
22

Gonçalves DF, Duarte T, Foletto JVP, et al. Mitochondrial function and cellular energy maintenance during aging in a Drosophila melanogaster model of Parkinson disease. Mitochondrion. 2022;65:166–175. https://doi.org/10.1016/j.mito.2022.06.007.
Crossref Google Scholar
23

Gan ZY, Callegari S, Cobbold SA, et al. Activation mechanism of PINK1. Nature. 2022;602(7896):328–335. https://doi.org/10.1038/s41586-021-04340-2.
Crossref Google Scholar
24

Fakih R, Sauve V, Gehring K. Feedforward activation of PRKN/parkin. Auto-phagy. 2023;19(2):729–730. https://doi.org/10.1080/15548627.2022.2100615.
Crossref Google Scholar
25

Araya J, Tsubouchi K, Sato N, et al. PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis. Autophagy. 2019;15(3):510–526. https://doi.org/10.1080/15548627.2018.1532259.
Crossref Google Scholar
26

Hou X, Chen TH, Koga S, et al. Alpha-synuclein-associated changes in PINK1-PRKN-mediated mitophagy are disease context dependent. Brain Pathol. 2023;33(5):e13175. https://doi.org/10.1111/bpa.13175.
Crossref Google Scholar
27

Yamada T, Dawson TM, Yanagawa T, et al. SQSTM1/p62 promotes mito-chondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019;15(11):2012–2018. https://doi.org/10.1080/15548627.2019.1643185.
Crossref Google Scholar
28

Zhu W, Huang XP, Yoon E, et al. Heterozygous PRKN mutations are common but do not increase the risk of Parkinson's disease. Brain. 2022;145(6): 2077–2091. https://doi.org/10.1093/brain/awab456.
Crossref Google Scholar
29

Chaikovsky AC, Li C, Jeng EE, et al. The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D. Nature. 2021;592(7856):794–798. https://doi.org/10.1038/s41586-021-03474-7.
Crossref Google Scholar
30

Maiani E, Milletti G, Nazio F, et al. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature. 2021;592(7856):799–803. https://doi.org/10.1038/s41586-021-03422-5.
Crossref Google Scholar
31

Gambarotto L, Metti S, Chrisam M, et al. Ambra1 deficiency impairs mitoph-agy in skeletal muscle. J Cachexia Sarcopenia Muscle. 2022;13(4):2211–2224. https://doi.org/10.1002/jcsm.13010.
Crossref Google Scholar
32

Spinazzi M, De Strooper B. PARL: the mitochondrial rhomboid protease. Semin Cell Dev Biol. 2016;60:19–28. https://doi.org/10.1016/j.semcdb.2016.07.034.
Crossref Google Scholar
33

Di Rienzo M, Romagnoli A, Ciccosanti F, et al. AMBRA1 regulates mitophagy by interacting with ATAD3A and promoting PINK1 stability. Autophagy. 2022;18(8):1752–1762. https://doi.org/10.1080/15548627.2021.1997052.
Crossref Google Scholar
34

Brunelli F, Torosantucci L, Gelmetti V, et al. PINK1 protects against staurosporine-induced apoptosis by interacting with Beclin1 and impairing its pro-apoptotic cleavage. Cells. 2022;11(4):678. https://doi.org/10.3390/cells11040678.
Crossref Google Scholar
35

Zhao YY, Hu D, Wang RH, et al. ATAD3A oligomerization promotes neuro-pathology and cognitive deficits in Alzheimer's disease models. Nat Commun. 2022;13(1):1121. https://doi.org/10.1038/s41467-022-28769-9.
Crossref Google Scholar
36

Zhao YY, Sun XY, Hu D, et al. ATAD3A oligomerization causes neuro-degeneration by coupling mitochondrial fragmentation and bioenergetics defects. Nat Commun. 2019;10(1):1371. https://doi.org/10.1038/s41467-019-09291-x.
Crossref Google Scholar
37

Watanabe S, Horiuchi M, Murata Y, et al. Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis. Neurobiol Dis. 2023;179:106031. https://doi.org/10.1016/j.nbd.2023.106031.
Crossref Google Scholar
38

Mårtensson CU, Priesnitz C, Song JY, et al. Mitochondrial protein translocation-associated degradation. Nature. 2019;569(7758):679–683. https://doi.org/10.1038/s41586-019-1227-y.
Crossref Google Scholar
39

Kato H, Lu QP, Rapaport D, Kozjak-Pavlovic V. Tom70 is essential for PINK1 import into mitochondria. PLoS One. 2013;8(3):1932–6203. https://doi.org/10.1371/journal.pone.0058435.
Crossref Google Scholar
40

Yang WL, Guo XY, Tu ZC, et al. PINK1 kinase dysfunction triggers neuro-degeneration in the primate brain without impacting mitochondrial homeostasis. Protein Cell. 2022;13(1):26–46. https://doi.org/10.1007/s13238-021-00888-x.
Crossref Google Scholar
41

Wasner K, Smajic S, Ghelfi J, et al. Parkin deficiency impairs mitochondrial DNA dynamics and propagates inflammation. Mov Disord. 2022;37(7): 1405–1415. https://doi.org/10.1002/mds.29025.
Crossref Google Scholar
42

Panicker N, Kam TI, Wang H, et al. Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease. Neuron. 2022;110(15): 2422–2437.e9. https://doi.org/10.1016/j.neuron.2022.05.009.
Crossref Google Scholar
43

Harbauer AB, Hees JT, Wanderoy S, et al. Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron. 2022;110(9):1516–1531.e9. https://doi.org/10.1016/j.neuron.2022.01.035.
Crossref Google Scholar
44

Hou W, Li GS, Gao L, et al. SYNJ2 is a novel and potential biomarker for the prediction and treatment of cancers: from lung squamous cell carcinoma to pan-cancer. BMC Med Genom. 2022;15(1):114. https://doi.org/10.1186/s12920-022-01266-0.
Crossref Google Scholar
45

Du QG, Guo XY, Zhang XY, et al. SYNJ2 variant Rs9365723 is associated with colorectal cancer risk in Chinese Han population. Int J Biol Markers. 2016;31(2):138–143. https://doi.org/10.5301/jbm.5000182.
Crossref Google Scholar
46

Abd Elghani F, Safory H, Hamza H, et al. SIAH proteins regulate the degra-dation and intra-mitochondrial aggregation of PINK1: implications for mito-chondrial pathology in Parkinson's disease. Aging Cell. 2022;21(12):e13731. https://doi.org/10.1111/acel.13731.
Crossref Google Scholar
47

Zhuang XX, Wang SF, Tan Y, et al. Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models. Cell Death Dis. 2020;11(2):128. https://doi.org/10.1038/s41419-020-2322-6.
Crossref Google Scholar
48

Segur-Bailach E, Ugarteburu O, Tort F, et al. Over-mutated mitochondrial, lysosomal and TFEB-regulated genes in Parkinson's disease. J Clin Med. 2022;11(6):1749. https://doi.org/10.3390/jcm11061749.
Crossref Google Scholar
49

Cheng FB, Zheng WX, Liu C, et al. Intronic enhancers of the human SNCA gene predominantly regulate its expression in brain in vivo. Sci Adv. 2022;8(47): eabq6324. https://doi.org/10.1126/sciadv.abq6324.
Crossref Google Scholar
50

Kon T, Forrest SL, Lee S, et al. Neuronal SNCA transcription during Lewy body formation. Acta Neuropathol Commun. 2023;11(1):185. https://doi.org/10.1186/s40478-023-01687-7.
Crossref Google Scholar
51

Fedotova EY, Iakovenko EV, Abramycheva NY, et al. SNCA gene methylation in Parkinson's disease and multiple system atrophy. Epigenomes. 2023;7(1):5. https://doi.org/10.3390/epigenomes7010005.
Crossref Google Scholar
52

Morales-Martínez A, Martínez-Gomez PA, Martinez-Fong D, et al. Oxidative stress and mitochondrial complex Ⅰ dysfunction correlate with neuro-degeneration in an a-synucleinopathy animal model. Int J Mol Sci. 2022;23(19):11394. https://doi.org/10.3390/ijms231911394.
Crossref Google Scholar
53

Eysert F, Kinoshita PF, Mary A, et al. Molecular dysfunctions of mitochondria-associated membranes (MAMs) in Alzheimer's disease. Int J Mol Sci. 2020;21(24):9521. https://doi.org/10.3390/ijms21249521.
Crossref Google Scholar
54

Tang YL, Li L, Hu TY, et al. In vivo 18F-florzolotau tau positron emission to-mography imaging in Parkinson's disease dementia. Mov Disord. 2023;38(1): 147–152. https://doi.org/10.1002/mds.29273.
Crossref Google Scholar
55

Bassil F, Meymand ES, Brown HJ, et al. a-Synuclein modulates tau spreading in mouse brains. J Exp Med. 2021;218(1):e20192193. https://doi.org/10.1084/jem.20192193.
Crossref Google Scholar
56

Chen X, He JL, Liu XT, et al. DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuro-inflammation. Neurobiol Stress. 2022;20:100486. https://doi.org/10.1016/j.ynstr.2022.100486.
Crossref Google Scholar
57

Yuan JX, Liu HH, Zhang H, et al. Controlled activation of TRPV1 channels on microglia to boost their autophagy for clearance of alpha-synuclein and enhance therapy of Parkinson's disease. Adv Mater. 2022;34(11):e2108435. https://doi.org/10.1002/adma.202108435.
Crossref Google Scholar
58

Wood H. Parkinson disease: peripheral a-synuclein deposits - prodromal markers for Parkinson disease? Nat Rev Neurol. 2016;12(5):249. https://doi.org/10.1038/nrneurol.2016.54.
Crossref Google Scholar
59

Lu J, Wang CF, Cheng X, et al. A breakdown in microglial metabolic reprog-ramming causes internalization dysfunction of a-synuclein in a mouse model of Parkinson's disease. J Neuroinflammation. 2022;19(1):113. https://doi.org/10.1186/s12974-022-02484-0.
Crossref Google Scholar
60

Park H, Kam TI, Peng HJ, et al. PAAN/MIF nuclease inhibition prevents neu-rodegeneration in Parkinson's disease. Cell. 2022;185(11):1943–1959.e21. https://doi.org/10.1016/j.cell.2022.04.020.
Crossref Google Scholar
61

Xin N, Durieux J, Yang CX, et al. The UPRmt preserves mitochondrial import to extend lifespan. J Cell Biol. 2022;221(7):e202201071. https://doi.org/10.1083/jcb.202201071.
Crossref Google Scholar
62

Kumar R, Chaudhary AK, Woytash J, et al. A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60. J Clin Invest. 2022;132(13):e149906. https://doi.org/10.1172/JCI149906.
Crossref Google Scholar
63

Wang Y, Jasper H, Toan S, et al. Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury. Redox Biol. 2021;45:102049. https://doi.org/10.1016/j.redox.2021.102049.
Crossref Google Scholar
64

Zhu L, Zhou QL, He L, et al. Mitochondrial unfolded protein response: an emerging pathway in human diseases. Free Radic Biol Med. 2021;163: 125–134. https://doi.org/10.1016/j.freeradbiomed.2020.12.013.
Crossref Google Scholar
65

Wang P, Deng JW, Dong J, et al. TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response. PLoS Genet. 2019;15(5):e1007947. https://doi.org/10.1371/journal.pgen.1007947.
Crossref Google Scholar
66

Berendzen KM, Durieux J, Shao LW, et al. Neuroendocrine coordination of mitochondrial stress signaling and proteostasis. Cell. 2016;166(6): 1553–1563.e10. https://doi.org/10.1016/j.cell.2016.08.042.
Crossref Google Scholar
67

Eesmaa A, Yu LY, Göös H, et al. CDNF interacts with ER chaperones and re-quires UPR sensors to promote neuronal survival. Int J Mol Sci. 2022;23(16): 9489. https://doi.org/10.3390/ijms23169489.
Crossref Google Scholar
68

Martinez BA, Petersen DA, Gaeta AL, et al. Dysregulation of the mitochondrial unfolded protein response induces non-apoptotic dopaminergic neuro-degeneration in C. elegans models of Parkinson's disease. J Neurosci. 2017;37(46):11085–11100. https://doi.org/10.1523/JNEUROSCI.1294-17.2017.
Crossref Google Scholar
69

Shpilka T, Haynes CM. The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat Rev Mol Cell Biol. 2018;19(2): 109–120. https://doi.org/10.1038/nrm.2017.110.
Crossref Google Scholar
70

Wang TS, Cao Y, Zheng Q, et al. SENP1-Sirt3 signaling controls mitochondrial protein acetylation and metabolism. Mol Cell. 2019;75(4):823–834.e5. https://doi.org/10.1016/j.molcel.2019.06.008.
Crossref Google Scholar
71

Xin T, Lu CZ. SirT3 activates AMPK-related mitochondrial biogenesis and ameliorates sepsis-induced myocardial injury. Aging. 2020;12(16): 16224–16237. https://doi.org/10.18632/aging.103644.
Crossref Google Scholar
72

Park JH, Burgess JD, Faroqi AH, et al. Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway. Mol Neuro-degener. 2020;15(1):5. https://doi.org/10.1186/s13024-019-0349-x.
Crossref Google Scholar
73

Gleave JA, Arathoon LR, Trinh D, et al. Sirtuin 3 rescues neurons through the stabilisation of mitochondrial biogenetics in the virally-expressing mutant a-synuclein rat model of Parkinsonism. Neurobiol Dis. 2017;106:133–146. https://doi.org/10.1016/j.nbd.2017.06.009.
Crossref Google Scholar
74

Nicholatos JW, Francisco AB, Bender CA, et al. Nicotine promotes neuron survival and partially protects from Parkinson's disease by suppressing SIRT6. Acta Neuropathol Commun. 2018;6(1):120. https://doi.org/10.1186/s40478-018-0625-y.
Crossref Google Scholar
75

Smirnov D, Eremenko E, Stein D, et al. SIRT6 is a key regulator of mitochon-drial function in the brain. Cell Death Dis. 2023;14(1):35. https://doi.org/10.1038/s41419-022-05542-w.
Crossref Google Scholar
76

Giacomello M, Pyakurel A, Glytsou C, et al. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol. 2020;21:204–224. https://doi.org/10.1038/s41580-020-0210-7.
Crossref Google Scholar
77

Soubannier V, McLelland GL, Zunino R, et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 2012;22(2): 135–141. https://doi.org/10.1016/j.cub.2011.11.057.
Crossref Google Scholar
78

König T, Nolte H, Aaltonen MJ, et al. MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat Cell Biol. 2021;23(12):1271–1286. https://doi.org/10.1038/s41556-021-00798-4.
Crossref Google Scholar
79

Lopez-Domenech G, Howden JH, Covill-Cooke C, et al. Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response. EMBO J. 2021;40(14):e100715. https://doi.org/10.15252/embj.2018100715.
Crossref Google Scholar
80

Hung CM, Lombardo PS, Malik N, et al. AMPK/ULK1-mediated phosphoryla-tion of Parkin ACT domain mediates an early step in mitophagy. Sci Adv. 2021;7(15):eabg4544. https://doi.org/10.1126/sciadv.abg4544.
Crossref Google Scholar
81

Schirinzi T, Salvatori I, Zenuni H, et al. Pattern of mitochondrial respiration in peripheral blood cells of patients with Parkinson's disease. Int J Mol Sci. 2022;23(18):10863. https://doi.org/10.3390/ijms231810863.
Crossref Google Scholar
82

Chen C, Mossman E, Malko P, et al. Astrocytic changes in mitochondrial oxidative phosphorylation protein levels in Parkinson's disease. Mov Disord. 2022;37(2):302–314. https://doi.org/10.1002/mds.28849.
Crossref Google Scholar
83

Bandara AB, Drake JC, James CC, et al. Complex Ⅰ protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics. Mitochondrion. 2021;58:160–168. https://doi.org/10.1016/j.mito.2021.03.003.
Crossref Google Scholar
84

Li HZ, Sun BH, Huang YT, et al. Gene therapy of yeast NDI1 on mitochondrial complex Ⅰ dysfunction in rotenone-induced Parkinson's disease models in vitro and vivo. Mol Med. 2022;28(1):29. https://doi.org/10.1186/s10020-022-00456-x.
Crossref Google Scholar
85

Funayama M, Ohe K, Amo TK, et al. CHCHD2 mutations in autosomal domi-nant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. Lancet Neurol. 2015;14(3):274–282. https://doi.org/10.1016/S1474-4422(14)70266-2.
Crossref Google Scholar
86

Ruan Y, Hu JQ, Che YP, et al. CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response. Cell Death Dis. 2022;13(2):156. https://doi.org/10.1038/s41419-022-04602-5.
Crossref Google Scholar
87

Lu L, Mao HX, Zhou MM, et al. CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson's disease. Chin Med J. 2022;135(13):1588–1596. https://doi.org/10.1097/cm9.0000000000002053.
Crossref Google Scholar
88

Sato S, Noda S, Torii S, et al. Homeostatic p62 levels and inclusion body for-mation in CHCHD2 knockout mice. Hum Mol Genet. 2021;30(6):443–453. https://doi.org/10.1093/hmg/ddab057.
Crossref Google Scholar
89

Nguyen MK, McAvoy K, Liao SC, et al. Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2. Hum Mol Genet. 2022;31(9):1500–1518. https://doi.org/10.1093/hmg/ddab329.
Crossref Google Scholar
90

Georgakopoulos ND, Wells G, Campanella M. The pharmacological regulation of cellular mitophagy. Nat Chem Biol. 2017;13:136–146. https://doi.org/10.1038/nchembio.2287.
Crossref Google Scholar
91

Ramalingam M, Huh YJ, Lee YI. The impairments of a-synuclein and mecha-nistic target of rapamycin in rotenone-induced SH-SY5Y cells and mice model of Parkinson's disease. Front Neurosci. 2019;13:1028. https://doi.org/10.3389/fnins.2019.01028.
Crossref Google Scholar
92

Oduro PK, Zheng XX, Wei JN, et al. The cGAS-STING signaling in cardiovascular and metabolic diseases: future novel target option for pharmacotherapy. Acta Pharm Sin B. 2022;12(1):50–75. https://doi.org/10.1016/j.apsb.2021.05.011.
Crossref Google Scholar
93

Xue CY, Dong N, Shan AS. Putative role of STING-mitochondria associated membrane crosstalk in immunity. Trends Immunol. 2022;43(7):513–522. https://doi.org/10.1016/j.it.2022.04.011.
Crossref Google Scholar
94

Han WH, Du CH, Zhu YG, et al. Targeting myocardial mitochondria-STING-polyamine axis prevents cardiac hypertrophy in chronic kidney disease. JACC Basic Transl Sci. 2022;7(8):820–840. https://doi.org/10.1016/j.jacbts.2022.03.006.
Crossref Google Scholar
95

West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17(6):363–375. https://doi.org/10.1038/nri.2017.21.
Crossref Google Scholar
96

Barnett KC, Coronas-Serna JM, Zhou W, et al. Phosphoinositide interactions position cGAS at the plasma membrane to ensure efficient distinction be-tween self- and viral DNA. Cell. 2019;176(6):1432–1446.e11. https://doi.org/10.1016/j.cell.2019.01.049.
Crossref Google Scholar
97

Hinkle JT, Patel J, Panicker N, et al. STING mediates neurodegeneration and neuroinflammation in nigrostriatal a-synucleinopathy. Proc Natl Acad Sci U S A. 2022;119(15):e2118819119. https://doi.org/10.1073/pnas.2118819119.
Crossref Google Scholar
98

Hancock-Cerutti W, Wu Z, Xu P, et al. ER-lysosome lipid transfer protein VPS13C/PARK23 prevents aberrant mtDNA-dependent STING signaling. J Cell Biol. 2022;221(7):e202106046. https://doi.org/10.1083/jcb.202106046.
Crossref Google Scholar
99

Weindel CG, Martinez EL, Zhao X, et al. Mitochondrial ROS promotes sus-ceptibility to infection via gasdermin D-mediated necroptosis. Cell. 2022;185(17):3214–3231.e23. https://doi.org/10.1016/j.cell.2022.06.038.
Crossref Google Scholar
100

Toyofuku T, Okamoto Y, Ishikawa T, et al. LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitina-tion pathway. EMBO J. 2020;39(2):e100875. https://doi.org/10.15252/embj.2018100875.
Crossref Google Scholar
101

Puigros M, Calderon A, Perez-Soriano A, et al. Cell-free mitochondrial DNA deletions in idiopathic, but not LRRK2, Parkinson's disease. Neurobiol Dis. 2022;174:105885. https://doi.org/10.1016/j.nbd.2022.105885.
Crossref Google Scholar
102

Müller-Nedebock AC, Meldau S, Lombard C, et al. Increased blood-derived mitochondrial DNA copy number in African ancestry individuals with Par-kinson's disease. Parkinsonism Relat Disorders. 2022;101:1–5. https://doi.org/10.1016/j.parkreldis.2022.06.003.
Crossref Google Scholar
103

Jennings D, Huntwork-Rodriguez S, Henry AG, et al. Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease. Sci Transl Med. 2022;14(648):eabj2658. https://doi.org/10.1126/scitranslmed.abj2658.
Crossref Google Scholar
104

Imberechts D, Kinnart I, Wauters F, et al. DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain. 2022;145(12): 4368–4384. https://doi.org/10.1093/brain/awac313.
Crossref Google Scholar
105

De Lazzari F, Agostini F, Plotegher N, et al. DJ-1 promotes energy balance by regulating both mitochondrial and autophagic homeostasis. Neurobiol Dis. 2023;176:105941. https://doi.org/10.1016/j.nbd.2022.105941.
Crossref Google Scholar
106

Czabotar PE, Garcia-Saez AJ. Mechanisms of BCL-2 family proteins in mito-chondrial apoptosis. Nat Rev Mol Cell Biol. 2023;24(10):732–748. https://doi.org/10.1038/s41580-023-00629-4.
Crossref Google Scholar
107

Liu J, Liu WJ, Lu YQ, et al. Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Par-kinson disease models. Autophagy. 2018;14(5):845–861. https://doi.org/10.1080/15548627.2017.1390636.
Crossref Google Scholar
108

Shanesazzade Z, Peymani M, Ghaedi K, et al. MiR-34a/BCL-2 signaling axis contributes to apoptosis in MPP(+)-induced SH-SY5Y cells. Mol Genet Genomic Med. 2018;6(6):975–981. https://doi.org/10.1002/mgg3.469.
Crossref Google Scholar
109

Offen D, Ziv I, Panet H, et al. Dopamine-induced apoptosis is inhibited in PC12 cells expressing bcl-2. Cell Mol Neurobiol. 1997;17(3):289–304. https://doi.org/10.1023/A:1026390201168.
Crossref Google Scholar
110

Park J, Lee SB, Lee S, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441(7097):1157–1161. https://doi.org/10.1038/nature04788.
Crossref Google Scholar
111

Han XJ, Liu Y, Dai Y, et al. Neuronal SH2B1 attenuates apoptosis in an MPTP mouse model of Parkinson's disease via promoting PLIN4 degradation. Redox Biol. 2022;52:102308. https://doi.org/10.1016/j.redox.2022.102308.
Crossref Google Scholar
112

Santucci R, Sinibaldi F, Cozza P, et al. Cytochrome c: an extreme multifunc-tional protein with a key role in cell fate. Int J Biol Macromol. 2019;136: 1237–1246. https://doi.org/10.1016/j.ijbiomac.2019.06.180.
Crossref Google Scholar
113

Shi JJ, Gao WQ, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 2017;42(4):245–254. https://doi.org/10.1016/j.tibs.2016.10.004.
Crossref Google Scholar
114

Li ZT, Mo FY, Wang YX, et al. Enhancing Gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments anti-tumor immune response. Nat Commun. 2022;13(1):6321. https://doi.org/10.1038/s41467-022-34036-8.
Crossref Google Scholar
115

He X, Fan XH, Bai B, et al. Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis. Pharmacol Res. 2021;165:105447. https://doi.org/10.1016/j.phrs.2021.105447.
Crossref Google Scholar
116

Lin J, Sun SH, Zhao K, et al. Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity. Nat Commun. 2023;14(1):224. https://doi.org/10.1038/s41467-023-35917-2.
Crossref Google Scholar
117

Wang YP, Gao WQ, Shi XY, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547(7661):99–103. https://doi.org/10.1038/nature22393.
Crossref Google Scholar
118

Ding JJ, Wang K, Liu W, et al. Pore-forming activity and structural auto-inhibition of the gasdermin family. Nature. 2016;535(7610):111–116. https://doi.org/10.1038/nature18590.
Crossref Google Scholar
119

Huang PT, Zhang ZY, Zhang P, et al. TREM2 deficiency aggravates NLRP3 inflammasome activation and pyroptosis in MPTP-induced Parkinson's dis-ease mice and LPS-induced BV2 cells. Mol Neurobiol. 2023:1–16. https://doi.org/10.1007/s12035-023-03713-0.
Crossref Google Scholar
120

Ryan SK, Zelic M, Han YN, et al. Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. Nat Neurosci. 2023;26(1):12–26. https://doi.org/10.1038/s41593-022-01221-3.
Crossref Google Scholar
121

Tian Y, Lu J, Hao XQ, et al. FTH1 inhibits ferroptosis through ferritinophagy in the 6-OHDA model of Parkinson's disease. Neurotherapeutics. 2020;17(4): 1796–1812. https://doi.org/10.1007/s13311-020-00929-z.
Crossref Google Scholar
122

Schulz V, Basu S, Freibert SA, et al. Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2. Nat Chem Biol. 2023;19(2): 206–217. https://doi.org/10.1038/s41589-022-01159-4.
Crossref Google Scholar
123

Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022;375(6586):1254–1261.
Crossref Google Scholar
124

Jiang ZY, Yin X, Wang M, et al. b-Hydroxybutyrate alleviates pyroptosis in MPPþ/MPTP-induced Parkinson's disease models via inhibiting STAT3/NLRP3/GSDMD pathway. Int Immunopharm. 2022;113:109451. https://doi.org/10.1016/j.intimp.2022.109451.
Crossref Google Scholar
125

Huan PF, Sun X, He ZQ, et al. Qiji Shujiang Granules alleviates dopaminergic neuronal injury of Parkinson's disease by inhibiting NLRP3/Caspase-1 pathway mediated pyroptosis. Phytomedicine. 2023;120:155019. https://doi.org/10.1016/j.phymed.2023.155019.
Crossref Google Scholar
126

Zhang X, Zhang YM, Li R, et al. Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis. Aging. 2020;12(10):9405–9426. https://doi.org/10.18632/aging.103215.
Crossref Google Scholar
127

Ma XX, Hao JN, Wu JR, et al. Prussian blue nanozyme as a pyroptosis inhibitor alleviates neurodegeneration. Adv Mater. 2022;34(15):e2106723. https://doi.org/10.1002/adma.202106723.
Crossref Google Scholar
128

Rui WJ, Li S, Xiao H, et al. Baicalein attenuates neuroinflammation by inhib-iting NLRP3/caspase-1/GSDMD pathway in MPTP-induced mice model of Parkinson's disease. Int J Neuropsychopharmacol. 2020;23(11):762–773. https://doi.org/10.1093/ijnp/pyaa060.
Crossref Google Scholar
129

Liu TY, Wang PH, Yin H, et al. Rapamycin reverses ferroptosis by increasing autophagy in MPTP/MPP+-induced models of Parkinson's disease. Neural Regen Res. 2023;18(11):2514–2519. https://doi.org/10.4103/1673-5374.371381.
Crossref Google Scholar
130

Lin ZH, Liu Y, Xue NJ, et al. Quercetin protects against MPP+/MPTP-induced dopaminergic neuron death in Parkinson's disease by inhibiting ferroptosis. Oxid Med Cell Longev. 2022;2022:7769355. https://doi.org/10.1155/2022/7769355.
Crossref Google Scholar
131

Chung I, Park HA, Kang J, et al. Neuroprotective effects of ATPase inhibitory factor 1 preventing mitochondrial dysfunction in Parkinson's disease. Sci Rep. 2022;12(1):3874. https://doi.org/10.1038/s41598-022-07851-8.
Crossref Google Scholar
Journal of Neurorestoratology
Volume 12 Issue 2,
June 2024
Article number: 100112
DOI: 10.1016/j.jnrt.2024.100112
Cite this article:
Yin S, Zhang Y, Wu J, et al. New perspectives on the role of mitochondria in Parkinson's disease. Journal of Neurorestoratology, 2024, 12(2): 100112. https://doi.org/10.1016/j.jnrt.2024.100112

174

Views

0

Crossref

0

Web of Science

0

Scopus

Altmetrics
Received: 16 October 2023
Revised: 06 January 2024
Accepted: 23 January 2024
Published: 16 March 2024
© 2024 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return