Fig. 7.

Mitochondrial ROS increased the survival of C. elegans fed on pathogenic E. coli via HIF-1 and AMPK. (A) isp-1(qm150) mutants lived longer than wild-type animals on hyperpathogenic E. coli. (B) hif-1(ia4) mutations partially suppressed the pathogen resistance of isp-1(qm150) (n = 2 of 3 trials). (Note that the hif-1 mutation itself tended to increase resistance against pathogenic E. coli, which appears to be dependent on DAF-16. See SI Appendix, Fig. S6 for details.) (C) aak-2(ok524) mutations significantly reduced the resistance of isp-1(qm150) mutants against pathogenic E. coli (n = 3). (Note that aak-2 mutants survived longer than wild-type animals on pathogenic E. coli; n = 2 of 3 trials.) Because aak-2 mutations displayed a tendency to increase ROS and hydrogen peroxide levels (Fig. 3 D–F), we speculate that increased ROS in aak-2 mutants upon hyperpathogenic E. coli infection may contribute to this enhanced pathogen resistance. (D–F) RNAi knockdown of dve-1 (D, n = 2), ubl-5 (E, n = 2), or ceh-23 (F, n = 2) had comparable effects on the pathogen resistance of isp-1 mutants and wild-type animals. (G) The proposed model shows how reduced respiration promotes longevity and immunity via a feedback mechanism involving HIF-1 and AMPK that regulates mitochondrial ROS. See SI Appendix, Table S6 for statistical analysis and additional repeats.