title: The Drosophila inner-membrane protein PMI controls crista biogenesis and mitochondrial diameter.
abstract: Cristae are mitochondrial inner-membrane structures that concentrate respiratory chain complexes and hence regulate ATP production. Mechanisms controlling crista morphogenesis are poorly understood and few crista determinants have been identified. Among them are the Mitofilins that are required to establish crista junctions and ATP-synthase subunits that bend the membrane at the tips of the cristae. We report here the phenotypic consequences associated with the in vivo inactivation of the inner-membrane protein Pantagruelian Mitochondrion I (PMI) both at the scale of the whole organism, and at the level of mitochondrial ultrastructure and function. We show that flies in which PMI is genetically inactivated experience synaptic defects and have a reduced life span. Electron microscopy analysis of the inner-membrane morphology demonstrates that loss of PMI function increases the average length of mitochondrial cristae in embryonic cells. This phenotype is exacerbated in adult neurons in which cristae form a dense tangle of elongated membranes. Conversely, we show that PMI overexpression is sufficient to reduce crista length in vivo. Finally, these crista defects are associated with impaired respiratory chain activity and increases in the level of reactive oxygen species. Since PMI and its human orthologue TMEM11 are regulators of mitochondrial morphology, our data suggest that, by controlling crista length, PMI influences mitochondrial diameter and tubular shape.
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille-Luminy, UMR 7288, F-13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Macchi
authors.forename: Najla
authors.initials: N
authors.lastname: El Fissi
authors.forename: Roberta
authors.initials: R
authors.lastname: Tufi
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bentobji
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Liévens
authors.forename: L Miguel
authors.initials: LM
authors.lastname: Martins
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
authors.forename: Thomas
authors.initials: T
authors.lastname: Rival
mesh_terms: D000818:Animals; D021961:Cell Membrane Structures / Q000235:genetics / Q000648:ultrastructure*; D019069:Cell Respiration / Q000235:genetics; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D055786:Gene Knockout Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000648:ultrastructure*; D053142:Mitochondrial Size / Q000235:genetics; D009474:Neurons / Q000648:ultrastructure*; D053140:Organelle Shape / Q000235:genetics; D030781:Organisms, Genetically Modified; D009435:Synaptic Transmission / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C561037:PMI protein, Drosophila