Splicing factor PRP-19 regulates mitochondrial stress response

Animals respond to mitochondrial perturbation by activating the mitochondrial unfolded protein response (UPR mt) to induce the transcription of mitochondrial stress response genes. In C. elegans, activation of UPR mt allows the animals to maintain organismal homeostasis, activate the innate immune response and promote lifespan extension. Here we show that splicing factors such as PRP-19 are required for the induction of UPR mt in C. elegans. PRP-19 also modulates mitochondrial perturbation-induced innate immune response and lifespan extension. Knockdown of PRP-19 in mammalian cells suppresses UPR mt activation and disrupts the mitochondrial network. These findings reveal an evolutionarily conserved mechanism that maintains mitochondrial homeostasis and controls innate immunity and lifespan through splicing factors.