Splitting up the powerhouse: structural insights into the mechanism of mitochondrial fission

Cell Mol Life Sci. 2015 Oct;72(19):3695-707. doi: 10.1007/s00018-015-1950-y. Epub 2015 Jun 10.

Abstract

Mitochondria are dynamic organelles whose shape is regulated by the opposing processes of fission and fusion, operating in conjunction with organelle distribution along the cytoskeleton. The importance of fission and fusion homeostasis has been highlighted by a number of disease states linked to mutations in proteins involved in regulating mitochondrial morphology, in addition to changes in mitochondrial dynamics in Alzheimer's, Huntington's and Parkinson's diseases. While a number of mitochondrial morphology proteins have been identified, how they co-ordinate to assemble the fission apparatus is not clear. In addition, while the master mediator of mitochondrial fission, dynamin-related protein 1, is conserved throughout evolution, the adaptor proteins involved in its mitochondrial recruitment are not. This review focuses on our current understanding of mitochondrial fission and the proteins that regulate this process in cell homeostasis, with a particular focus on the recent mechanistic insights based on protein structures.

Keywords: Adaptors; Dynamin-related protein 1; Endoplasmic reticulum; Fission; Lipids; Mitochondria; Outer mitochondrial membrane.

Publication types

  • Review

MeSH terms

  • Cardiolipins / metabolism
  • Dynamins
  • Endoplasmic Reticulum / physiology*
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / metabolism*
  • Homeostasis / physiology*
  • Humans
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Models, Molecular*
  • Plakins / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • Cardiolipins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Plakins
  • Reactive Oxygen Species
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins