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Amyotrophic Lateral Sclerosis (ALS): Stressed by Dysfunctional Mitochondria-Endoplasmic Reticulum Contacts (MERCs)

1
Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada
2
Department of Medicine (Neurology), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada
*
Author to whom correspondence should be addressed.
Academic Editors: Nica Borgese and Francesca Navone
Cells 2021, 10(7), 1789; https://doi.org/10.3390/cells10071789
Received: 7 May 2021 / Revised: 12 July 2021 / Accepted: 13 July 2021 / Published: 15 July 2021
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which there is currently no cure. Progress in the characterization of other neurodegenerative mechanisms has shifted the spotlight onto an intracellular structure called mitochondria-endoplasmic reticulum (ER) contacts (MERCs) whose ER portion can be biochemically isolated as mitochondria-associated membranes (MAMs). Within the central nervous system (CNS), these structures control the metabolic output of mitochondria and keep sources of oxidative stress in check via autophagy. The most relevant MERC controllers in the ALS pathogenesis are vesicle-associated membrane protein-associated protein B (VAPB), a mitochondria-ER tether, and the ubiquitin-specific chaperone valosin containing protein (VCP). These two systems cooperate to maintain mitochondrial energy output and prevent oxidative stress. In ALS, mutant VAPB and VCP take a central position in the pathology through MERC dysfunction that ultimately alters or compromises mitochondrial bioenergetics. Intriguingly, both proteins are targets themselves of other ALS mutant proteins, including C9orf72, FUS, or TDP-43. Thus, a new picture emerges, where different triggers cause MERC dysfunction in ALS, subsequently leading to well-known pathological changes including endoplasmic reticulum (ER) stress, inflammation, and motor neuron death. View Full-Text
Keywords: mitochondria-associated membranes (MAMs); amyotrophic lateral sclerosis (ALS); mitochondria-endoplasmic reticulum contacts (MERCs) mitochondria-associated membranes (MAMs); amyotrophic lateral sclerosis (ALS); mitochondria-endoplasmic reticulum contacts (MERCs)
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MDPI and ACS Style

Chen, J.; Bassot, A.; Giuliani, F.; Simmen, T. Amyotrophic Lateral Sclerosis (ALS): Stressed by Dysfunctional Mitochondria-Endoplasmic Reticulum Contacts (MERCs). Cells 2021, 10, 1789. https://doi.org/10.3390/cells10071789

AMA Style

Chen J, Bassot A, Giuliani F, Simmen T. Amyotrophic Lateral Sclerosis (ALS): Stressed by Dysfunctional Mitochondria-Endoplasmic Reticulum Contacts (MERCs). Cells. 2021; 10(7):1789. https://doi.org/10.3390/cells10071789

Chicago/Turabian Style

Chen, Junsheng, Arthur Bassot, Fabrizio Giuliani, and Thomas Simmen. 2021. "Amyotrophic Lateral Sclerosis (ALS): Stressed by Dysfunctional Mitochondria-Endoplasmic Reticulum Contacts (MERCs)" Cells 10, no. 7: 1789. https://doi.org/10.3390/cells10071789

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