New insights into the function and regulation of mitochondrial fission

Biochim Biophys Acta. 2013 May;1833(5):1256-68. doi: 10.1016/j.bbamcr.2013.02.002. Epub 2013 Feb 20.

Abstract

Mitochondrial morphology changes dynamically by coordinated fusion and fission and cytoskeleton-based transport. Cycles of outer and inner membrane fusion and fission are required for the exchange of damaged mitochondrial genome DNA, proteins, and lipids with those of healthy mitochondria to maintain robust mitochondrial structure and function. These dynamics are crucial for cellular life and death, because they are essential for cellular development and homeostasis, as well as apoptosis. Disruption of these functions leads to cellular dysfunction, resulting in neurologic disorders and metabolic diseases. The cytoplasmic dynamin-related GTPase Drp1 plays a key role in mitochondrial fission, while Mfn1, Mfn2 and Opa1 are involved in fusion reaction. Here, we review current knowledge regarding the regulation and physiologic relevance of Drp1-dependent mitochondrial fission: the initial recruitment and assembly of Drp1 on the mitochondrial fission foci, regulation of Drp1 activity by post-translational modifications, and the role of mitochondrial fission in cell pathophysiology.

Publication types

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

MeSH terms

  • Apoptosis / physiology
  • Cytoskeleton* / metabolism
  • Cytoskeleton* / ultrastructure
  • GTP Phosphohydrolases* / chemistry
  • GTP Phosphohydrolases* / genetics
  • GTP Phosphohydrolases* / metabolism
  • Humans
  • Membrane Fusion / physiology
  • Microtubule-Associated Proteins* / chemistry
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Microtubule-Associated Proteins* / physiology
  • Mitochondria* / metabolism
  • Mitochondria* / physiology
  • Mitochondria* / ultrastructure
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / physiology
  • Mitochondrial Proteins* / chemistry
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism
  • Protein Processing, Post-Translational / genetics

Substances

  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • DNM1L protein, human