Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis
ABSTRACT Defects of the mitochondria have been implicated in many diseases. Due to the diverse set of mitochondrial functions, many proteins must be imported into the organelle, properly folded, and assembled into large complexes with proper stoichiometry. Failure in any of these processes is disastrous, as unfolding, misfolding, or even improper numbers of proteins may cause loss of function of the organelle. Accordingly, several mitochondrial quality control mechanisms exist, which ensure homeostasis within the organelle. Many – if not all – of these quality control machineries have been shown to functionally decline during the aging process, making mitochondrial quality control an intriguing aspect in our understanding of aging. Over the last decade, we have discovered, using the genetically-tractable nematode C. elegans, that mitochondrial dysfunction in neurons, is capable of eliciting long-range effects of inducing the UPRmt in distal tissues, which has direct implications on org