Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism

Publication date: 5 June 2018
Source:Cell Reports, Volume 23, Issue 10
Author(s): Julie Lavie, Harmony De Belvalet, Sessinou Sonon, Ana Madalina Ion, Elodie Dumon, Su Melser, Didier Lacombe, Jean-William Dupuy, Claude Lalou, Giovanni Bénard
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.

Graphical abstract

Teaser

Lavie et al. show that ubiquitin-dependent degradation of key mitochondrial proteins regulates mitochondrial energy metabolism and that turnover of several key proteins is dependent upon the ubiquitin proteasome system (UPS). These findings support the idea that ubiquitin-dependent degradation is directly involved in the regulation of mitochondrial energy metabolism.


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