Mitochondrial recovery by the UPRmt: Insights from C. elegans

Mitochondria are multifaceted organelles, with such functions as the production of cellular energy to the regulation of cell death. However, mitochondria incur various sources of damage from the accumulation of reactive oxygen species and DNA mutations that can impact the protein folding environment and impair their function. Since mitochondrial dysfunction is often associated with reductions in organismal fitness and possibly disease, cells must have safeguards in place to protect mitochondrial function and promote recovery during times of stress. The mitochondrial unfolded protein response (UPRmt) is a transcriptional adaptation that promotes mitochondrial repair to aid in cell survival during stress. While the earlier discoveries into the regulation of the UPRmt stemmed from studies using mammalian cell culture, much of our understanding about this stress response has been bestowed to us by the model organism Caenorhabditis elegans. Indeed, the facile but powerful genetics of this relatively simple nematode has uncovered multiple regulators of the UPRmt, as well as several physiological roles of this stress response. In this review, we will summarize these major advancements originating from studies using C. elegans.