Abstract
Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Mitochondria are highly dynamic organelles that undergo continuous fusion, fission, and transport, the processes of which not only control mitochondrial morphology and number but also regulate mitochondrial function and location. The importance of mitochondrial dynamics in the pathogenesis of neurodegenerative diseases has been increasingly unraveled after the identification of several key fusion and fission regulators such as Drp1, OPA1, and mitofusins. In this review, after a brief discussion of molecular mechanisms regulating mitochondrial fusion, fission, distribution, and trafficking, as well as the important role of mitochondrial dynamics for neuronal function, we review previous and the most recent studies about mitochondrial dynamic abnormalities observed in various major neurodegenerative diseases and discuss the possibility of targeting mitochondrial dynamics as a likely novel therapeutic strategy for neurodegenerative diseases.
Highlights
IntroductionMitochondria are organelles that can be found in most eukaryotic cells and are required for a wide range of cellular processes such as the generation of cellular adenosine triphosphate (ATP), the synthesis of key metabolites, the production of endogenous reactive oxygen species, Ca2+
Mitochondria are organelles that can be found in most eukaryotic cells and are required for a wide range of cellular processes such as the generation of cellular adenosine triphosphate (ATP), the synthesis of key metabolites, the production of endogenous reactive oxygen species, Ca2+hemostasis, and programmed and unprogrammed cell death [1,2,3]
As cellular metabolism and mitochondria are closely related, these findings suggest that mitochondrial dysfunction likely plays a central role in the pathogenesis of neurodegenerative diseases
Summary
Mitochondria are organelles that can be found in most eukaryotic cells and are required for a wide range of cellular processes such as the generation of cellular adenosine triphosphate (ATP), the synthesis of key metabolites, the production of endogenous reactive oxygen species, Ca2+. The brain, at only 2% of the body weight, consumes about 20% of the body’s energy [4] Due to their limited glycolytic capacity and extremely metabolically active nature, neurons in the brain are energetically demanding cells requiring the delicate maintenance of mitochondrial function [5]. Mitochondria are highly dynamic organelles that undergo continual fusion and fission events, which maintain their integrity and quantity, and serve crucial mitochondrial functions such as ATP production [10], Ca2+ homeostasis [11,12], cell death [13,14,15], and reactive oxygen species (ROS) production [16]. Recent findings of widespread mitochondrial fragmentation, along with altered distribution in cell bodies and neuronal processes in common neurodegenerative diseases [17,18], suggest that abnormal mitochondrial fusion, fission, and trafficking dynamics may contribute to mitochondrial dysfunction and neurodegeneration in these devastating diseases. We will focus on the role of mitochondria dynamic abnormalities in a number of common neurodegenerative diseases
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