Mutations that result in a mild impairment of mitochondrial function can extend longevity. Previous studies have shown that the increase in lifespan is dependent on stress responsive transcription factors, including DAF-16/FOXO, which exhibits increased nuclear localization in long-lived mitochondrial mutants. We recently found that the localization of DAF-16 within the cell is dependent on the endosomal trafficking protein TBC-2. Based on the important role of DAF-16 in both longevity and resistance to stress, we examined the effect of disruptingtbc-2on lifespan and stress resistance in the long-lived mitochondrial mutantsnuo-6andisp-1inCaenorhabditis elegans. Loss oftbc-2markedly reduced the long lifespans of both mitochondrial mutants. Disruption oftbc-2also decreased resistance to chronic oxidative stress innuo-6andisp-1mutants but had little or no detrimental effect on resistance to other stressors. In contrast,tbc-2inhibition had no effect on oxidative stress resistance or lifespan inisp-1worms when DAF-16 is absent, suggesting that the effect oftbc-2on mitochondrial mutant lifespan may be mediated by mislocalization of DAF-16. However, this result is complicated by the fact that deletion ofdaf-16markedly decreases both phenotypes inisp-1worms, which could result in a floor effect. In exploring the contribution of DAF-16 further, we found that disruption oftbc-2did not affect the nuclear localization of DAF-16 inisp-1worms or prevent the upregulation of DAF-16 target genes in the long-lived mitochondrial mutants. This suggests the possibility that the effect oftbc-2on lifespan and stress resistance in the long-lived mitochondrial mutants is at least partially independent of its effects on DAF-16 localization. Overall, this work demonstrates the importance of endosomal trafficking for the extended longevity and enhanced stress resistance resulting from mild impairment of mitochondrial function.