Abstract / Summary
In response to constant homeostatic threats, organisms have developed complex regulatory networks to monitor cellular functions and restore normal function. Here, we identify MDT-15 and its effectors, the fatty acid desaturases FAT-5, FAT-6, and FAT-7, as activators of the Ethanol and Stress Response (ESRE) mitochondrial surveillance pathway. Our data show that box C/D snoRNPs, which were previously linked to ESRE activation, also regulate FAT-6 and FAT-7 protein levels. Notably, knockdown of mdt-15 or fib-1 , a component of the box C/D snoRNP complex, increased accumulation of the mitophagic activator PINK-1, the first step in licensing mitophagy, suggesting a relationship between ESRE surveillance and mitophagic activation. Our results show that both MDT-15 and FAT-6 are required for host defense against liquid-based Pseudomonas aeruginosa pathogenesis, linking this mitochondrial surveillance network to resistance against acute infection. Supplementation with downstream unsaturated fatty acid products of FAT-6 and FAT-7 enhanced ESRE and mitophagic activation, but did not affect the mitochondrial unfolded protein response (UPR mt ) pathway. Since fatty acids activated ESRE and PINK-1 in wild-type and mutant genetic backgrounds, they are likely to act via a mechanism independent of FAT-6 and FAT-7 function. Our results provide insight into a novel interplay between box C/D snoRNPs, MDT-15, and fatty acids in the regulation of mitochondrial surveillance, mitophagy, and host defense.