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 Caenorhabditis 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 Precursor RNA processing 19(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.