Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases

J Biochem. 2014 May;155(5):273-9. doi: 10.1093/jb/mvu016. Epub 2014 Mar 9.


Accumulating evidence indicate physiological significance of mitochondrial dynamics such as mitochondrial fusion and division, the dynamic movement of mitochondria along microtubules and interaction of mitochondria with the endoplasmic reticulum. A disruption in mitochondrial dynamics leads to a functional deterioration of mitochondria, resulting in a variety of diseases including neurodegenerative disorders. We previously identified a mitochondrial ubiquitin ligase MITOL/MARCH5, which belongs to the membrane-associated RING-CH E3 ubiquitin ligase (MARCH) family (also called MARCH5). MITOL plays an important role in the regulation of mitochondrial dynamics including mitochondrial morphology, transport and interaction with ER, at least in part, through the ubiquitinations of mitochondrial fission factor Drp1, microtubule-associated protein 1B and mitofusin2, respectively. This review focuses on recent findings that show how MITOL regulates mitochondrial dynamics and which suggest physiological disorders resulting from a failure in such regulation.

Keywords: MAM; MAP1B; S-nitrosylation; mitochondrial dynamics; ubiquitin ligase.

Publication types

  • Review

MeSH terms

  • Animals
  • Dynamins
  • Endoplasmic Reticulum / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Protein Denaturation
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • MARCHF5 protein, human
  • Ubiquitin-Protein Ligases
  • GTP Phosphohydrolases
  • MFN2 protein, human
  • DNM1L protein, human
  • Dynamins