ROS-based lethality ofC. elegansmitochondrial electron transport mutants grown onE. colisiderophore iron release mutants

Abstract

AbstractC. elegansconsumes bacteria which can supply essential vitamins and cofactors especially for mitochondrial functions ancestrally related to bacteria. Therefore, we screened the KeioE. coliknockout library for mutations that induce aC. elegansmitochondrial damage response gene. We identified 45E. colimutations that induce a theC. elegans hsp-6::gfpresponse gene. Surprisingly, four of theseE. colimutations that disrupt the import or removal of iron from the bacterial siderophore enterobactin were lethal in combination withC. elegansmutations that disrupt particular iron-sulfur proteins of the electron transport chain. Bacterial mutations that fail to synthesize enterobactin are not synthetic lethal with theseC. elegansmitochondrial mutants; it is the enterobactin-iron complex that is lethal in combination with theC. elegansmitochondrial mutations. Antioxidants suppress this inviability, suggesting that reactive oxygen species (ROS) are produced by the mutant mitochondria in combination with the bacterial enterobactin-iron complex.Significance StatementThe animal mitochondrion has a bacterial origin and continues to have a dialogue with the bacterial metabolisms of their microbiome. We identified 45E. coligene disruptions that induce aC. elegansmitochondrial damage response gene. Four of theseE. colimutations that disrupt the import or retrieval of iron from the siderophore enterobactin were synthetic lethal withC. elegansmitochondrial mutants. Antioxidants strongly suppressed the inviability ofC. elegansmitochondrial mutants grown on theE. colienterobactin siderophore utilization or import mutants. We hypothesize that reactive oxygen species are produced by C. elegans mitochondrial mutations and that this non-lethal ROS triggers ferric-chelated enterobactin to induce dramatically increased ROS, which leads to lethality.