文摘
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Summary
Mitochondria maintain cellular homeostasis by coordinating ATP synthesis with metabolic activity, redox signaling, and apoptosis. Excessive levels of聽mitochondria-derived reactive oxygen species (ROS) promote mitochondrial dysfunction, triggering numerous metabolic disorders. However, the molecular basis for聽the harmful effects of excessive ROS formation is largely unknown. Here, we identify a聽link between mitochondrial stress and ubiquitin-dependent proteolysis, which supports cellular surveillance both in聽Caenorhabditis elegans and humans. Worms defective in respiration with elevated ROS levels are limited聽in turnover of a GFP-based substrate protein, demonstrating that mitochondrial聽stress affects the聽ubiquitin/proteasome system (UPS). Intriguingly, we聽observed similar proteolytic defects for disease-causing IVD and COX1 mutations associated with mitochondrial failure in humans. Together, these results identify a conserved link between mitochondrial metabolism and ubiquitin-dependent proteostasis. Reduced UPS activity during pathological conditions might potentiate disease progression and thus provides a valuable target for therapeutic intervention.
