Synergistic Roles of FAHD-1 and PYC-1 in Mitochondrial Function, Behavior, and Longevity in C. elegans.

ABSTRACT: Mitochondrial metabolism plays a central role in organismal physiology and aging. In Caenorhabditis elegans, FAHD-1 (oxaloacetate decarboxylase) and PYC-1 (pyruvate carboxylase) catalyze opposing reactions that influence oxaloacetate homeostasis within the tricarboxylic acid cycle. To dissect their functional interplay, we analyzed single- and double-knockout strains generated by CRISPR/Cas9 alongside the classical allele. Fahd-1 mutants exhibit impaired mitochondrial respiration, reduced motility, and early egg-laying onset, whereas pyc-1 mutants display increased locomotion and enhanced metabolic flexibility. Paradoxically, although each single mutantion extended lifespan, combining them restored wild-type lifespan and partially normalized respiratory function, suggesting a compensatory

SUBMITTER: Giaquinta R 

PROVIDER: S-EPMC12817237 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature