SUMOylation modulates mitochondrial unfolded protein response Kaiyu Gao1, Yi Li1,2, Shumei Hu1,2, Ying Liu1* 1Institute or Organization State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; 2Institute or Organization Academy of Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China *Corresponding Author
Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (mitoUPR) to promote fitness. Upon mitoUPR activation, a cascade of events occurs and ultimately triggers a transcriptional response governed by two transcription factors: DVE-1 and ATFS-1. Here we identify SUMO-specific peptidase ULP-4 as a positive regulator of C. elegans mitoUPR to control SUMOylation status of DVE-1 and ATFS-1 during mitochondrial dysfunction. SUMO modulates these two axes in the transcriptional program of mitoUPR with distinct mechanisms: change of subcellular localization vs. change of stability and activity. Our findings reveal a post-translational modification that promotes immune response and lifespan extension during mitochondrial stress.
Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Peking-Tsinghua Center for Life Sciences, Howard Hughes Medical Institute