Mitochondria, the power plants of the cell, are the evolved descendants of ancient symbiotic bacteria. They have a small remnant mitochondrial genome, but over time most of the proteins necessary to mitochondrial function migrated to the nuclear genome. Such proteins are produced in the normal way in and around the cell nucleus, and are then imported into mitochondria for use. Researchers here investigate how this import system relates to longevity, finding that it can be adjusted in ways that influence quality control mechanisms and other aspects of mitochondrial metabolism.
Sustained mitochondrial fitness relies on coordinated biogenesis and clearance via mitophagy. Both processes are regulated by constant targeting of proteins into the organelle. Thus, mitochondrial protein import sets the pace for mitochondrial abundance and function. However, our understanding of mitochondrial protein translocation as a regulator of longevity remains enigmatic. Here, we targeted the main protein import translocases and assessed their contribution to mitochondrial abundance and organismal physiology.
We find that reduction in cellular mitochondrial load through mitochondrial protein import system suppression, referred to as MitoMISS, elicits a distinct longevity paradigm. We show that MitoMISS triggers the mitochondrial unfolded protein response (UPRmt), orchestrating an adaptive reprogramming of metabolism. Glycolysis and de novo serine biosynthesis are causatively linked to longevity, whilst mitochondrial chaperone induction is dispensable for lifespan extension. Our findings extent the pro-longevity role of UPRmt and provide insight, relevant to the metabolic alterations that promote or undermine survival and longevity.