Xia Peixue, Zhou Liankui, Guan Jialiang, Ding Wanqiu, Liu Ying
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Life Metab. 2022 Jun 24;1(1):81-93. doi: 10.1093/lifemeta/loac009. eCollection 2022 Aug.
Animals respond to mitochondrial perturbation by activating the mitochondrial unfolded protein response (UPR) to induce the transcription of mitochondrial stress response genes. In , activation of UPR 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 in . PRP-19 also modulates mitochondrial perturbation-induced innate immune response and lifespan extension. Knockdown of PRP-19 in mammalian cells suppresses UPR 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.
动物通过激活线粒体未折叠蛋白反应（UPR）来应对线粒体扰动，以诱导线粒体应激反应基因的转录。在[具体情境未提及]中，UPR的激活使动物能够维持机体稳态、激活先天免疫反应并促进寿命延长。在此，我们表明，诸如前体RNA加工19（PRP-19）等剪接因子是[具体情境未提及]中UPR诱导所必需的。PRP-19还调节线粒体扰动诱导的先天免疫反应和寿命延长。在哺乳动物细胞中敲低PRP-19会抑制UPR激活并破坏线粒体网络。这些发现揭示了一种进化上保守的机制，该机制通过剪接因子维持线粒体稳态并控制先天免疫和寿命。
