Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism.

Lavie et al. show that turnover of several key proteins is dependent upon the ubiquitin proteasome system (UPS). Notably, degradation of subunit A of the succinate dehydrogenase (SDHA) through this mechanism modify mitochondrial energy metabolism. These findings demonstrate that mitochondrial internal functions are also regulated by UPS. These results are published in Cell Reports (Lavie J et al. 2018) DOI: https://doi.org/10.1016/j.celrep.2018.05.013

(A) Sub-mitochondrial localization of K48 conjugates analyzed by western blot. Sub-mitochondrial compartments (OMM, IMM, and matrix [Mx]) were obtained from HeLa cells treated with vehicle, MG132, or epoxomicin. MFN2, ATP5A, and ATAD3A are respective markers of the OMM, Mx, and IMM.

(B) Effect of MG132 on the accumulation of Myc-SDHA, Myc-SDHAK179R (K179), Myc-SDHAK541R (K541), and Myc-SDHAK179R,K541R analyzed by western blot. HeLa cells were labeled as no transfection (NT) or transfected with mutant or WT Myc-SDHA and treated with MG132 (8 hr). Expression of ectopic SDHA was revealed using an anti-Myc antibody.

(C) Levels of different cellular metabolites analyzed in HeLa cells transfected with Myc-SDHA (light bars) or Myc-SDHAK179R,K541R (dark bars) (n = 3–4). *p < 0.05, two-way ANOVA and multiple-comparison test.