Mitochondrial Quality Control Pathways Sense Mitochondrial Protein Import

Mitochondrial quality control (MQC) mechanisms are required to maintain a functional proteome, which enables mitochondria to perform a myriad of important cellular functions from oxidative phosphorylation to numerous metabolic pathways. Mitochondrial protein homeostasis begins with the import of over 1000 nuclear-encoded mitochondrial proteins, and the synthesis of 13 mitochondrial DNA-encoded proteins. A network of chaperones and proteases helps to fold new proteins and degrade unnecessary, damaged or misfolded proteins. Meanwhile, more extensive damage can be removed by mitochondrial derived vesicles or mitochondrial autophagy (mitophagy). Here, we review the importance of mitochondrial protein import as a sentinel of mitochondrial function that activates multiple MQC mechanisms when impaired, with a focus on mechanisms in mammalian cells.