Mitochondrial fusion/fission Dynamics in Neurodegeneration and Neuronal Plasticity

Neurobiol Dis. 2016 Jun;90:3-19. doi: 10.1016/j.nbd.2015.10.011. Epub 2015 Oct 19.

Abstract

Mitochondria are dynamic organelles that continually move, fuse and divide. The dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs, keeps mitochondria in good health by restoring or removing damaged organelles or precipitates cells in apoptosis in cases of severe defects. Mitochondrial fusion and fission are essential in mammals and their disturbances are associated with several diseases. However, while mitochondrial fusion/fission dynamics, and the proteins that control these processes, are ubiquitous, associated diseases are primarily neurological disorders. Accordingly, inactivation of the main actors of mitochondrial fusion/fission dynamics is associated with defects in neuronal development, plasticity and functioning, both ex vivo and in vivo. Here, we present the central actors of mitochondrial fusion and fission and review the role of mitochondrial dynamics in neuronal physiology and pathophysiology. Particular emphasis is placed on the three main actors of these processes i.e. DRP1,MFN1-2, and OPA1 as well as on GDAP1, a protein of the mitochondrial outer membrane preferentially expressed in neurons. This article is part of a Special Issue entitled: Mitochondria & Brain.

Keywords: Axon; Charcot–Marie–Tooth disease; DRP1; Dendrite; Dominant Optic Atrophy; GDAP1; MFN1; MFN2; Mitochondria; Mitochondrial fission; Mitochondrial fusion; Neurodegeneration; Neuronal maturation; Neuronal plasticity; OPA1; Synapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics / physiology*
  • Neurodegenerative Diseases / metabolism*
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism