Mitochondrial Quality Control in Amyotrophic Lateral Sclerosis: Towards a Common Pathway?

Overview

Journal Neural Regen Res

Date 2017 Aug 31

PMID 28852382

Citations 25

Authors

Bilal Khalil

Jean-Charles Lievens

Affiliations

Soon will be listed here.

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by loss of upper and lower motor neurons. Different mechanisms contribute to the disease initiation and progression, including mitochondrial dysfunction which has been proposed to be a central determinant in ALS pathogenesis. Indeed, while mitochondrial defects have been mainly described in ALS-linked SOD1 mutants, it is now well established that mitochondria become also dysfunctional in other ALS conditions. In such context, the mitochondrial quality control system allows to restore normal functioning of mitochondria and to prevent cell death, by both eliminating and replacing damaged mitochondrial components or by degrading the entire organelle through mitophagy. Recent evidence shows that ALS-related genes interfere with the mitochondrial quality control system. This review highlights how ineffective mitochondrial quality control may render motor neurons defenseless towards the accumulating mitochondrial damage in ALS.

Citing Articles

A pathogenic mutation in the ALS/FTD gene VCP induces mitochondrial hypermetabolism by modulating the permeability transition pore.

Vanderhaeghe S, Prerad J, Tharkeshwar A, Goethals E, Vints K, Beckers J Acta Neuropathol Commun. 2024; 12(1):161.

PMID: 39390590 PMC: 11465669. DOI: 10.1186/s40478-024-01866-0.

Aberrant protein aggregation in amyotrophic lateral sclerosis.

Wang H, Zeng R J Neurol. 2024; 271(8):4826-4851.

PMID: 38869826 DOI: 10.1007/s00415-024-12485-z.

Molecular hallmarks of ageing in amyotrophic lateral sclerosis.

Jagaraj C, Shadfar S, Kashani S, Saravanabavan S, Farzana F, Atkin J Cell Mol Life Sci. 2024; 81(1):111.

PMID: 38430277 PMC: 10908642. DOI: 10.1007/s00018-024-05164-9.

Mitochondria: A Promising Convergent Target for the Treatment of Amyotrophic Lateral Sclerosis.

Cunha-Oliveira T, Montezinho L, Simoes R, Carvalho M, Ferreiro E, Silva F Cells. 2024; 13(3.

PMID: 38334639 PMC: 10854804. DOI: 10.3390/cells13030248.

Putative Roles and Therapeutic Potential of the Chaperone System in Amyotrophic Lateral Sclerosis and Multiple Sclerosis.

Noori L, Saqagandomabadi V, Di Felice V, David S, Caruso Bavisotto C, Bucchieri F Cells. 2024; 13(3.

PMID: 38334609 PMC: 10854686. DOI: 10.3390/cells13030217.

References

Soubannier V, McLelland G, Zunino R, Braschi E, Rippstein P, Fon E . A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 2012; 22(2):135-41. DOI: 10.1016/j.cub.2011.11.057. View

Stoica R, De Vos K, Paillusson S, Mueller S, Sancho R, Lau K . ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun. 2014; 5:3996. PMC: 4046113. DOI: 10.1038/ncomms4996. View

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

Renton A, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs J . A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011; 72(2):257-68. PMC: 3200438. DOI: 10.1016/j.neuron.2011.09.010. View

Margineantu D, Emerson C, Diaz D, Hockenbery D . Hsp90 inhibition decreases mitochondrial protein turnover. PLoS One. 2007; 2(10):e1066. PMC: 2031825. DOI: 10.1371/journal.pone.0001066. View

McLelland G, Soubannier V, Chen C, McBride H, Fon E . Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014; 33(4):282-95. PMC: 3989637. DOI: 10.1002/embj.201385902. View

Morotz G, De Vos K, Vagnoni A, Ackerley S, Shaw C, Miller C . Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria. Hum Mol Genet. 2012; 21(9):1979-88. PMC: 3315205. DOI: 10.1093/hmg/dds011. View

Kimura Y, Fukushi J, Hori S, Matsuda N, Okatsu K, Kakiyama Y . Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system. Genes Cells. 2013; 18(12):1131-43. DOI: 10.1111/gtc.12103. View

Yamashita H, Kawamata J, Okawa K, Kanki R, Nakamizo T, Hatayama T . Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS. J Neurochem. 2007; 102(5):1497-1505. DOI: 10.1111/j.1471-4159.2007.04534.x. View

10.

Fukada K, Zhang F, Vien A, Cashman N, Zhu H . Mitochondrial proteomic analysis of a cell line model of familial amyotrophic lateral sclerosis. Mol Cell Proteomics. 2004; 3(12):1211-23. PMC: 1360176. DOI: 10.1074/mcp.M400094-MCP200. View

11.

Vande Velde C, McDonald K, Boukhedimi Y, McAlonis-Downes M, Lobsiger C, Bel Hadj S . Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. PLoS One. 2011; 6(7):e22031. PMC: 3136936. DOI: 10.1371/journal.pone.0022031. View

12.

Gegg M, Cooper J, Chau K, Rojo M, Schapira A, Taanman J . Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 2010; 19(24):4861-70. PMC: 3583518. DOI: 10.1093/hmg/ddq419. View

13.

Kane L, Lazarou M, Fogel A, Li Y, Yamano K, Sarraf S . PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014; 205(2):143-53. PMC: 4003245. DOI: 10.1083/jcb.201402104. View

14.

Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H . Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria. Biochem Biophys Res Commun. 2002; 300(2):482-93. DOI: 10.1016/s0006-291x(02)02874-7. View

15.

Chen Y, Deng J, Wang P, Yang M, Chen X, Zhu L . PINK1 and Parkin are genetic modifiers for FUS-induced neurodegeneration. Hum Mol Genet. 2016; 25(23):5059-5068. PMC: 6078632. DOI: 10.1093/hmg/ddw310. View

16.

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier C . PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010; 189(2):211-21. PMC: 2856912. DOI: 10.1083/jcb.200910140. View

17.

Roberts R, Tang M, Fon E, Durcan T . Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles. Int J Biochem Cell Biol. 2016; 79:427-436. DOI: 10.1016/j.biocel.2016.07.020. View

18.

ARLT H, Steglich G, Perryman R, Guiard B, Neupert W, Langer T . The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease. EMBO J. 1998; 17(16):4837-47. PMC: 1170813. DOI: 10.1093/emboj/17.16.4837. View

19.

Twig G, Elorza A, Molina A, Mohamed H, Wikstrom J, Walzer G . Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008; 27(2):433-46. PMC: 2234339. DOI: 10.1038/sj.emboj.7601963. View

20.

Song Z, Chen H, Fiket M, Alexander C, Chan D . OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 2007; 178(5):749-55. PMC: 2064540. DOI: 10.1083/jcb.200704110. View