1. Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways
- Author
-
Pascale Belenguer, Julien Royet, Frédéric Maillet, Laetitia Arnauné-Pelloquin, Marc Macchi, Mickael Poidevin, Thomas Rival, Fabrice Richard, and Ahmed Fatmi
- Subjects
Dynamins ,endocrine system ,animal structures ,Microtubule-associated protein ,Mitochondrion ,Biochemistry ,Mitochondrial Membrane Transport Proteins ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Mitochondrial membrane transport protein ,GTP-binding protein regulators ,GTP-Binding Proteins ,Genetics ,Morphogenesis ,Animals ,Drosophila Proteins ,Humans ,RNA, Small Interfering ,Molecular Biology ,Cells, Cultured ,biology ,Scientific Reports ,Lipid bilayer fusion ,Membrane Proteins ,Membrane Transport Proteins ,Cell biology ,Mitochondria ,Cytoskeletal Proteins ,Membrane protein ,mitochondrial fusion ,Gene Knockdown Techniques ,Mitochondrial Membranes ,biology.protein ,Mitochondrial fission ,Drosophila ,Carrier Proteins ,Microtubule-Associated Proteins - 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.
- Published
- 2010