Lavie 2018 Cell Rep
|Lavie J, De Belvalet H, Sonon S, Ion AM, Dumon E, Melser S, Lacombe D, Dupuy JW, Lalou C, Bénard G (2018) Ubiquitin-dependent degradation of mitochondrial proteins regulates energy metabolism. Cell Rep 23:2852-63.|
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.
• Keywords: Mitochondrial energy metabolism, Succinate dehydrogenase, Ubiquitin • Bioblast editor: Kandolf G
Labels: MiParea: Respiration, mt-Membrane
Organism: Human Tissue;cell: HeLa Preparation: Intact cells