Mechanisms Through Which Some Mitochondria-Generated Metabolites Act as Second Messengers That Are Essential Contributors to the Aging Process in Eukaryotes Across Phyla

Conclusions In this review, we analyzed mechanisms through which mitobolites, a distinct set of mitochondria-generated metabolites, can be released from mitochondria and then act as second messengers that contribute to cellular and organismal aging by regulating longevity-defining processes outside of mitochondria. Our analysis indicates that in eukaryotes across phyla, these second messengers of cellular aging exhibit the following common features: (1) they are produced in mitochondria in response to certain changes in the nutrient, stress, proliferation or age status of the cell; it remains unknown, however, what kind of protein sensors can respond to such changes by transmitting the signal to mitochondria so that mitochondria can increase the rates of catabolic and anabolic reactions producing these mitobolites; (2) their release from mitochondria and delivery to different non-mitochondrial locations within the cell also depend on these changes in the nutrient, stress, proliferation or age status of the cell; and (3) in cellular locations outside of mitochondria, they activate or inhibit a distinct set of protein sensors that in response set up a pro- or anti-aging cellular pattern by changing the efficiencies of certain pro- or anti-aging cellular processes; for some mitobolites, the identities of such protein sensors and/or mechanisms of their action are presently unknown. One important challenge is to define molecular mechanisms underlying the protein-mediated signalin...
Source: Frontiers in Physiology - Category: Physiology Source Type: research