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

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.
Mesh Terms:
Animals, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Drosophila, Drosophila Proteins, GTP Phosphohydrolases, GTP-Binding Proteins, Gene Knockdown Techniques, Humans, Membrane Proteins, Membrane Transport Proteins, Microtubule-Associated Proteins, Mitochondria, Mitochondrial Membrane Transport Proteins, Mitochondrial Membranes, Mitochondrial Proteins, Morphogenesis, RNA, Small Interfering
EMBO Rep.
Date: Mar. 01, 2011
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