Mitochondrial Fusion: The Machineries In and Out

Trends Cell Biol. 2021 Jan;31(1):62-74. doi: 10.1016/j.tcb.2020.09.008. Epub 2020 Oct 19.


Mitochondria are highly dynamic organelles that constantly undergo fission and fusion. Disruption of mitochondrial dynamics undermines their function and causes several human diseases. The fusion of the outer (OMM) and inner mitochondrial membranes (IMM) is mediated by two classes of dynamin-like protein (DLP): mitofusin (MFN)/fuzzy onions 1 (Fzo1) and optic atrophy 1/mitochondria genome maintenance 1 (OPA1/Mgm1). Given the lack of structural information on these fusogens, the molecular mechanisms underlying mitochondrial fusion remain unclear, even after 20 years. Here, we review recent advances in structural studies of the mitochondrial fusion machinery, discuss their implication for DLPs, and summarize the pathogenic mechanisms of disease-causing mutations in mitochondrial fusion DLPs.

Keywords: Dynamin superfamily; Mitofusin/Fzo1; OPA1/Mgm1; cristae formation; mitochondrial fusion; structure.

Publication types

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

MeSH terms

  • Dynamins / metabolism
  • Humans
  • Membrane Fusion
  • Mitochondrial Dynamics*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism
  • Structural Homology, Protein


  • Mitochondrial Proteins
  • Dynamins