Coordinating Mitochondrial Biology Through the Stress-Responsive Regulation of Mitochondrial Proteases

Proteases are localized throughout mitochondria and function as critical regulators of all aspects of mitochondrial biology. As such, the activities of these proteases are sensitively regulated through transcriptional and post-translational mechanisms to adapt mitochondrial function to specific cellular demands. Here, we discuss the stress-responsive mechanisms responsible for regulating mitochondrial protease activity and the implications of this regulation on mitochondrial function. Furthermore, we describe how imbalances in the activity or regulation of mitochondrial proteases induced by genetic, environmental, or aging-related factors influence mitochondria in the context of disease. Understanding the molecular mechanisms by which cells regulate mitochondrial function through alterations in protease activity provide insights into the contributions of these proteases in pathologic mitochondrial dysfunction and reveals new therapeutic opportunities to ameliorate this dysfunction in the context of diverse classes of human disease.