Noncanonical role of MTP-18 in mitochondrial function and aging via electron transport chain interactions in Caenorhabditis elegans.

Abstract

Mitochondria provide energy and maintain homeostasis, and their dysfunction relates to aging. Disrupted structure and function of mitochondria are linked to age-related diseases, but the roles of many mitochondrial proteins in mitochondrial dynamics and aging remain unclear. We studied the role of the mitochondrial fission protein MTP-18 in mitochondrial dynamics and aging in C. elegans. Our data show that loss of mtp-18 increases longevity and stress resistance, alongside changes in key physiological processes. We tested whether mtp-18-mediated longevity is linked to the PI3K-dependent insulin/IGF-1 signaling (IIS) pathway. mtp-18-mediated longevity requires the Forkhead transcription factor DAF-16, a primary effector of the IIS pathway, but is not mediated by the canonical IIS cascade. We also observed unique interactions between mtp-18 and genes encoding components of the mobile electron carrier system in mitochondria, such as coenzyme Q and cytochrome c. Our study reveals that mtp-18 is an evolutionarily conserved, key aging regulator that maintains mitochondrial morphology. What sets this study apart from previous research is the identification of a novel mechanism by which MTP-18 affects these processes independently of the canonical IIS pathway, particularly through unique interactions with genes encoding components of the electron transport chain.