What Is the Role of Mitochondrial Fission in Neurologic Disease?

Abstract

Mitochondria have multiple essential functions in cells, including energy production through oxidative phosphorylation, calcium and reactive oxygen species (ROS) signaling, biosynthesis of nucleotides, amino acids, and lipids, and apoptosis. Mitochondria exist as a network of highly dynamic organelles and may be present in multiple shapes and sizes within the cell. Mitochondrial shape and dynamics, including the balance between mitochondrial fusion and fission, critically affect mitochondrial function and their abnormalities have been increasingly recognized as an important disease mechanism. As a major example, excessive mitochondrial fission leading to fragmentation of the mitochondrial network, mitochondrial dysfunction, and oxidative stress has been implicated in multiple neurodegenerative diseases including Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS), as well as in cancer, cardiomyopathies, and metabolic and renal disorders. There are recent comprehensive reviews on this topic.1-5 The identification of the main components of the mitochondrial fission machinery and the mechanisms leading to their excessive activation have led to neuroprotective approaches that have proven effective in disease models.