The art of mitochondrial maintenance

SUMMARY

The maintenance of a healthy and functional mitochondrial network is critical during development as well as throughout life to respond to physiological adaptations and to cope with stress. Owing to their role in energy production, mitochondria are exposed to high amounts of reactive oxygen species making them particularly vulnerable to mitochondrial DNA mutations and protein misfolding. Given that mitochondria are formed from proteins encoded by both nuclear and mitochondrial genomes, an additional layer of complexity is inherent in the coordination of protein synthesis and nuclear encoded protein import. For these reasons mitochondria have evolved multiple systems of quality control to ensure that the requisite number of functional mitochondria are present to meet the demands of the cell. These pathways work to eliminate damaged mitochondrial proteins or parts of the mitochondrial network by mitophagy and renew components by adding protein and lipids through biogenesis, collectively resulting in mitochondrial turnover. Mitochondrial quality control mechanisms are multi-tiered, operating at the protein, organelle and cell level. Herein, we discuss mitophagy in different physiological contexts and then relate it to other quality control pathways including the unfolded protein response, shedding of vesicles, proteolysis and degradation by the ubiquitin-proteasome system. Understanding how these pathways contribute to the maintenance of mitochondrial homeostasis may lead to insights in the development of targeted treatments when these systems fail in disease.