Splicing factor PRP-19 regulates mitochondrial stress response

Abstract

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.

Keywords

mitochondria / unfolded protein response / stress response / splicing / lifespan

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The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.