Brain Mitochondria, Aging, and Parkinson's Disease

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2018 May 13

PMID 29751692

Citations 25

Authors

Mario Rango

Nereo Bresolin

Affiliations

Soon will be listed here.

Abstract

This paper reconsiders the role of mitochondria in aging and in Parkinson's Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered autophagy, and mitochondrial dysfunction. Beyond declined oxidative phosphorylation, mitochondrial dysfunction consists of a decline of beta-oxidation as well as of the Krebs cycle. Not inherited mitochondrial DNA (mtDNA) mutations are acquired over time and parallel the decrease in oxidative phosphorylation. Many of these mitochondrial alterations are also found in the PD brain specifically in the substantia nigra (SN). mtDNA deletions and development of respiratory chain deficiency in SN neurons of aged individuals as well as of individuals with PD converge towards a shared pathway, which leads to neuronal dysfunction and death. Finally, several nuclear genes that are mutated in hereditary PD are usually implicated in mitochondrial functioning to a various extent and their mutation may cause mitochondrial impairment. In conclusion, a tight link exists between mitochondria, aging, and PD.

Citing Articles

α-Synuclein Degradation in Brain Pericytes Is Mediated via Akt, ERK, and p38 MAPK Signaling Pathways.

Yokoya M, Takata F, Iwao T, Matsumoto J, Tanaka Y, Aridome H Int J Mol Sci. 2025; 26(4).

PMID: 40004079 PMC: 11855147. DOI: 10.3390/ijms26041615.

Mitophagy and cGAS-STING crosstalk in neuroinflammation.

Zhou X, Wang J, Yu L, Qiao G, Qin D, Law B Acta Pharm Sin B. 2024; 14(8):3327-3361.

PMID: 39220869 PMC: 11365416. DOI: 10.1016/j.apsb.2024.05.012.

Exploring the complexity of EEG patterns in Parkinson's disease.

Nucci L, Miraglia F, Pappalettera C, Rossini P, Vecchio F Geroscience. 2024; 47(1):837-849.

PMID: 38997574 PMC: 11872966. DOI: 10.1007/s11357-024-01277-y.

Paving the way while playing catch up: mitochondrial genetics in African ancestry primary open-angle glaucoma.

Kuang G, Salowe R, OBrien J Front Ophthalmol (Lausanne). 2024; 3():1267119.

PMID: 38983031 PMC: 11182247. DOI: 10.3389/fopht.2023.1267119.

Predictors associated with the rate of progression of nigrostriatal degeneration in Parkinson's disease.

Yoo H, Kim H, Lee H, Yoon S, Na H, Kang S J Neurol. 2024; 271(8):5213-5222.

PMID: 38839638 DOI: 10.1007/s00415-024-12477-z.

References

Biskup S, Moore D . Detrimental deletions: mitochondria, aging and Parkinson's disease. Bioessays. 2006; 28(10):963-7. DOI: 10.1002/bies.20471. View

Miller K, Sheetz M . Axonal mitochondrial transport and potential are correlated. J Cell Sci. 2004; 117(Pt 13):2791-804. DOI: 10.1242/jcs.01130. View

Theurey P, Pizzo P . The Aging Mitochondria. Genes (Basel). 2018; 9(1). PMC: 5793175. DOI: 10.3390/genes9010022. View

Mehta P, Mellick G, Rowe D, Halliday G, Jones M, Manwaring N . Mitochondrial DNA haplogroups J and K are not protective for Parkinson's disease in the Australian community. Mov Disord. 2008; 24(2):290-2. DOI: 10.1002/mds.22389. View

Phillipson O . Management of the aging risk factor for Parkinson's disease. Neurobiol Aging. 2013; 35(4):847-57. DOI: 10.1016/j.neurobiolaging.2013.10.073. View

Ekstrand M, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E . Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci U S A. 2007; 104(4):1325-30. PMC: 1783140. DOI: 10.1073/pnas.0605208103. View

Wyss-Coray T . Ageing, neurodegeneration and brain rejuvenation. Nature. 2016; 539(7628):180-186. PMC: 5172605. DOI: 10.1038/nature20411. View

Krishnan K, Reeve A, Samuels D, Chinnery P, Blackwood J, Taylor R . What causes mitochondrial DNA deletions in human cells?. Nat Genet. 2008; 40(3):275-9. DOI: 10.1038/ng.f.94. View

Song L, Shan Y, Lloyd K, Cortopassi G . Mutant Twinkle increases dopaminergic neurodegeneration, mtDNA deletions and modulates Parkin expression. Hum Mol Genet. 2012; 21(23):5147-58. PMC: 3607469. DOI: 10.1093/hmg/dds365. View

10.

Ross J, Olson L, Coppotelli G . Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?. Int J Mol Sci. 2015; 16(8):19458-76. PMC: 4581307. DOI: 10.3390/ijms160819458. View

11.

Shi H, Deng H, Gius D, Schumacker P, Surmeier D, Ma Y . Sirt3 protects dopaminergic neurons from mitochondrial oxidative stress. Hum Mol Genet. 2017; 26(10):1915-1926. PMC: 6075394. DOI: 10.1093/hmg/ddx100. View

12.

Devi L, Raghavendran V, Prabhu B, Avadhani N, Anandatheerthavarada H . Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008; 283(14):9089-100. PMC: 2431021. DOI: 10.1074/jbc.M710012200. View

13.

Wang X, Petrie T, Liu Y, Liu J, Fujioka H, Zhu X . Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction. J Neurochem. 2012; 121(5):830-9. PMC: 3740560. DOI: 10.1111/j.1471-4159.2012.07734.x. View

14.

Geldenhuys W, Benkovic S, Lin L, Yonutas H, Crish S, Sullivan P . MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype. ACS Chem Neurosci. 2017; 8(12):2759-2765. PMC: 5964979. DOI: 10.1021/acschemneuro.7b00287. View

15.

Stevens D, Lee Y, Kang H, Lee B, Lee Y, Bower A . Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci U S A. 2015; 112(37):11696-701. PMC: 4577198. DOI: 10.1073/pnas.1500624112. View

16.

Chinnery P . Mitochondrial disease in adults: what's old and what's new?. EMBO Mol Med. 2015; 7(12):1503-12. PMC: 4693502. DOI: 10.15252/emmm.201505079. View

17.

Bobela W, Aebischer P, Schneider B . Αlpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson's Disease. Biomolecules. 2015; 5(4):2675-700. PMC: 4693253. DOI: 10.3390/biom5042675. View

18.

Betarbet R, Sherer T, MacKenzie G, Panov A, Greenamyre J . Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000; 3(12):1301-6. DOI: 10.1038/81834. View

19.

Horvath R, Kley R, Lochmuller H, Vorgerd M . Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNALys. Neurology. 2007; 68(1):56-8. DOI: 10.1212/01.wnl.0000250334.48038.7a. View

20.

Vincow E, Merrihew G, Thomas R, Shulman N, Beyer R, MacCoss M . The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc Natl Acad Sci U S A. 2013; 110(16):6400-5. PMC: 3631677. DOI: 10.1073/pnas.1221132110. View