Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways

EMBO Rep. 2011 Mar;12(3):223-30. doi: 10.1038/embor.2010.214. Epub 2011 Jan 28.

Abstract

Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Dynamins
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / ultrastructure*
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Morphogenesis / genetics
  • RNA, Small Interfering

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Microtubule-Associated Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • OPA1 protein, Drosophila
  • PMI protein, Drosophila
  • RNA, Small Interfering
  • peptidoglycan recognition protein
  • DRP1 protein, Drosophila
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Mfn1 protein, human
  • DNM1L protein, human
  • Dynamins