Mitochondrial aconitase inhibits immunity via reducing mitochondrial unfolded protein response

We show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We found that genetic inhibition of aco-2 enhanced mitochondrial unfolded protein response, subsequently upregulating ATFS-1 transcription factor, which contributed to enhanced immunity against pathogenic bacteria. The investigation of the changes of gene expression upon knockdown of aco-2 or infection with PA14.

本研究表明，线粒体顺乌头酸酶ACO-2（mitochondrial aconitase, ACO-2）作为一种催化柠檬酸向异柠檬酸转化的三羧酸循环（Krebs cycle）酶，可抑制秀丽隐杆线虫（C. elegans）对病原菌的免疫防御。研究发现，对aco-2基因实施遗传抑制可激活线粒体未折叠蛋白反应（mitochondrial unfolded protein response），进而上调转录因子ATFS-1的表达，该效应有助于增强秀丽隐杆线虫对抗病原菌的免疫能力。本研究还分析了aco-2基因敲低或经PA14菌株感染后，基因表达的变化情况。