Mitochondrial redox homeostasis links organellar stress surveillance to germline and somatic integrity in Caenorhabditis elegans

Despite the induction of a stress response at the transcriptional level, gsr-1a trxr-2 double mutants maintained normal respiration, ATP and ROS production, and were not more resistant to oxidative or pathogen stressors. In turn, mitochondrial morphology was altered in a tissue-specific manner, with elongated networks in muscle cells while more fragmented in hypodermis. These changes were independent of mitophagy but sensitive to disruption of mitochondrial fission or fusion machinery, highlighting the importance of dynamic remodeling of the mitochondrial network for survival in animals with impaired mitochondrial redox homeostasis.

Functionally, gsr-1a trxr-2 mutants showed impaired motility, reduced calcium uptake upon carbachol stimulation, enhanced hypodermal wound repair, and decreased fertilization efficiency associated with lower muscle exopher production. Overall, our data show that mitochondrial GSR-1a and TRXR-2 act redundantly to preserve redox balance in this organelle. Their simultaneous loss triggers a constitutive ATFS-1–dependent UPRmt that sustains viability but compromises growth, fertility, and muscle performance, revealing mitochondrial redox control as a core determinant of organismal homeostasis.