Mitochondrial proteases modulate mitochondrial stress signalling and cellular homeostasis in health and disease

Maintenance of mitochondrial homeostasis requires a plethora of coordinated quality control and adaptations’ mechanisms in which mitochondrial proteases play a key role. Their activation or loss of function reverberate beyond local mitochondrial biochemical and metabolic remodelling into coordinated cellular pathways and stress responses that feedback onto the mitochondrial functionality and adaptability. Mitochondrial proteolysis modulates molecular and organellar quality control, metabolic adaptations, lipid homeostasis and regulates transcriptional stress responses. Defective mitochondrial proteolysis results in disease conditions most notably, mitochondrial diseases, neurodegeneration and cancer. Here, it will be discussed how mitochondrial proteases and mitochondria stress signalling impact cellular homeostasis and determine the cellular decision to survive or die, how these processes may impact disease etiopathology, and how modulation of proteolysis may offer novel therapeutic strategies.