Cytosolic Proteostasis Networks of the Mitochondrial Stress Response

Mitochondrial stress requires timely intervention to prevent mitochondria' and cellular dysfunction. Re-establishing the correct protein homeostasis is crucial for coping with mitochondria' stress and maintaining cellular homeostasis. The best-characterized adaptive pathways for mitochondria' stress involve a signal originating from stressed mitochondria that triggers a nuclear response. However, recent findings have shown that mitochondria' stress also affects a complex network of protein homeostasis pathways in the cytosol. We review how mitochondria' dysregulation affects cytosolic proteostasis by regulating the quantity and quality of protein synthesis, protein stability, and protein degradation, leading to an integrated regulation of cellular metabolism and proliferation. This mitochondria to cytosol network extends the current model of the mitochondria' stress response, with potential applications in the treatment of mitochondria' disease.