title: Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.
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.
authors.affiliation: Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR 6216/Aix-Marseille Universités, F-13288 Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rival
authors.forename: Marc
authors.initials: M
authors.lastname: Macchi
authors.forename: Laetitia
authors.initials: L
authors.lastname: Arnauné-Pelloquin
authors.forename: Mickael
authors.initials: M
authors.lastname: Poidevin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maillet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Richard
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fatmi
authors.forename: Pascale
authors.initials: P
authors.lastname: Belenguer
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000648:ultrastructure*; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis / Q000235:genetics; D034741:RNA, Small Interfering
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C527116:OPA1 protein, Drosophila; C561037:PMI protein, Drosophila; D034741:RNA, Small Interfering; C118897:peptidoglycan recognition protein; C504426:DRP1 protein, Drosophila; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C470017:Mfn1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins