Impaired mitochondrial dynamics in disease

Mitochondria are highly dynamic organelles, which rapidly undergo fusion and fission events in response to a broad suite of physiological conditions, including cell cycle progression, differentiation, and stress. The term “mitochondrial dynamics” captures the mechanisms that regulate mitochondrial biogenesis and degradation; distribution of mitochondria via trafficking cytoskeletal proteins; connectivity through coordinated fusion and fission events; and intercellular transfer of mitochondria through tunneling nanotubes. The recognition that dysregulation of these events is associated with neurodegenerative diseases, including Charcot-Marie Tooth 2A, autosomal dominant optic atrophy, and Parkinson’s disease, has increased the intensity of research to understand and manipulate them. The maintenance and modulation of mitochondrial dynamic function is also implicated in ischemic-reperfusion injury and several cancers. Here, we discuss the molecular mechanisms that govern mitochondrial fusion, fission, and distribution. We briefly address roles in health and disease, including new therapeutic interventions and new computational tools to quantitatively assess mitochondrial dynamics and network morphology.