1. Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism
- Author
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Ana Madalina Ion, Jean-William Dupuy, Didier Lacombe, Su Melser, Harmony De Belvalet, Sessinou Sonon, Elodie Dumon, Claude Lalou, Julie Lavie, Giovanni Benard, Université de Bordeaux (UB), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), U1211 Laboratoire Maladies Rares: Génétique et Métabolisme, Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, and Laboratoire Maladies Rares : Génétique et Métabolisme [Bordeaux] (MRGM)
- Subjects
0106 biological sciences ,Proteasome Endopeptidase Complex ,[SDV]Life Sciences [q-bio] ,Biophysics ,Energy metabolism ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,01 natural sciences ,Biochemistry ,Mitochondrial Proteins ,03 medical and health sciences ,Ubiquitin ,Humans ,Mitochondrial protein ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Ubiquitination ,Cell Biology ,Cell biology ,Mitochondria ,Succinate Dehydrogenase ,Protein Subunits ,Proteolysis ,biology.protein ,Degradation (geology) ,Energy Metabolism ,010606 plant biology & botany ,HeLa Cells - Abstract
The ubiquitin proteasome system (UPS) regulates many cellular functions by degrading key proteins. Notably, the role of UPS in regulating mitochondrial metabolic functions is unclear. Here, we show that ubiquitination occurs in different mitochondrial compartments, including the inner mitochondrial membrane, and that turnover of several metabolic proteins is UPS dependent. We specifically detailed mitochondrial ubiquitination and subsequent UPS-dependent degradation of succinate dehydrogenase subunit A (SDHA), which occurred when SDHA was minimally involved in mitochondrial energy metabolism. We demonstrate that SDHA ubiquitination occurs inside the organelle. In addition, we show that the specific inhibition of SDHA degradation by UPS promotes SDHA-dependent oxygen consumption and increases ATP, malate, and citrate levels. These findings suggest that the mitochondrial metabolic machinery is also regulated by the UPS.
- Published
- 2017
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