title: Rheb regulates mitophagy induced by mitochondrial energetic status.
abstract: Mitophagy has been recently described as a mechanism of elimination of damaged organelles. Although the regulation of the amount of mitochondria is a core issue concerning cellular energy homeostasis, the relationship between mitochondrial degradation and energetic activity has not yet been considered. Here, we report that the stimulation of mitochondrial oxidative phosphorylation enhances mitochondrial renewal by increasing its degradation rate. Upon high oxidative phosphorylation activity, we found that the small GTPase Rheb is recruited to the mitochondrial outer membrane. This mitochondrial localization of Rheb promotes mitophagy through a physical interaction with the mitochondrial autophagic receptor Nix and the autophagosomal protein LC3-II. Thus, Rheb-dependent mitophagy contributes to the maintenance of optimal mitochondrial energy production. Our data suggest that mitochondrial degradation contributes to a bulk renewal of the organelle in order to prevent mitochondrial aging and to maintain the efficiency of oxidative phosphorylation.
authors.affiliation: EA4576, Maladies Rares: Génétique et Métabolisme, 33000 Bordeaux Cedex, France.
authors.forename: Su
authors.initials: S
authors.lastname: Melser
authors.forename: Etienne Hébert
authors.initials: EH
authors.lastname: Chatelain
authors.forename: Julie
authors.initials: J
authors.lastname: Lavie
authors.forename: Walid
authors.initials: W
authors.lastname: Mahfouf
authors.forename: Caroline
authors.initials: C
authors.lastname: Jose
authors.forename: Emilie
authors.initials: E
authors.lastname: Obre
authors.forename: Susan
authors.initials: S
authors.lastname: Goorden
authors.forename: Muriel
authors.initials: M
authors.lastname: Priault
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Rezvani
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bénard
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020559:Monomeric GTP-Binding Proteins