Mortal engines: Mitochondrial bioenergetics and dysfunction in neurodegenerative diseases

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Amit U Joshi, Daria Mochly-Rosen

Abstract

Mitochondria are best known for their role in ATP generation. However, studies over the past two decades have shown that mitochondria do much more than that. Mitochondria regulate both necrotic and apoptotic cell death pathways, they store and therefore coordinate cellular Ca2+ signaling, they generate and metabolize important building blocks, by-products and signaling molecules, and they also generate and are targets of free radical species that modulate many aspects of cell physiology and pathology. Most estimates suggest that although the brain makes up only 2 percent of body weight, utilizes about 20 percent of the body's total ATP. Thus, mitochondrial dysfunction greatly impacts brain functions and is indeed associated with numerous neurodegenerative diseases. Furthermore, a number of abnormal disease-associated proteins have been shown to interact directly with mitochondria, leading to mitochondrial dysfunction and subsequent neuronal cell death. Here, we discuss the role of mitochondrial dynamics impairment in the pathological processes associated with neurodegeneration and suggest that a therapy targeting mitochondrialdysfunction holds a great promise.

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Citations

Feb 1, 2020·Reviews in the Neurosciences·Haym Benaroya
Aug 20, 2019·Journal of Neuroscience Research·Theodore A SarafianJoseph B Watson
Sep 5, 2020·International Journal of Molecular Sciences·Leonora SzaboAmandine Grimm
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May 16, 2020·Frontiers in Physiology·Zhenhong FuYundai Chen
Nov 5, 2019·Molecular and Cellular Neurosciences·Kevin McAvoy, Hibiki Kawamata
Feb 2, 2021·Frontiers in Molecular Neuroscience·Magdalena CieślikAgata Adamczyk
Feb 28, 2021·Mitochondrion·Rishabh JhanjiSimona Bungau
Sep 29, 2021·CNS & Neurological Disorders Drug Targets·Ramin Ahangar-SirousNiloofar Deravi

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