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Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. Previously, we determined that decreased expression of the cytosolic pentose phosphate pathway (PPP) enzyme transaldolase activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan. Here we report that transaldolase (tald-1) deficiency impairs mitochondrial function in vivo, as evidenced by altered mitochondrial morphology, decreased respiration, and increased cellular H2O2 levels. Lifespan extension from knockdown of tald-1 is associated with an oxidative stress response involving p38 and c-Jun N-terminal kinase (JNK) MAPKs and a starvation-like response regulated by the transcription factor EB (TFEB) homolog HLH-30. The latter response promotes autophagy and increases expression of the flavin-containing monooxygenase 2 (fmo-2). We conclude that cytosolic redox established through the PPP is a key regulator of mitochondrial function and defines a new mechanism for mitochondrial regulation of longevity., Author summary There are a growing number of studies linking mitochondrial dysfunction to enhanced longevity, especially in the nematode C. elegans. The reasons for these pro-longevity effects have been elusive, but one current model is that adaptive responses to mitochondrial inhibition promote organismal health and stress resistance. Here, we report an intriguing example of mitochondrial stress induced by inhibition of a cytosolic metabolic pathway that extends lifespan in worms. We find that inhibition of the pentose phosphate pathway, which is essential for cytosolic redox homeostasis, affects multiple parameters of mitochondrial function and activates a starvation-like response that promotes longevity through recycling of damaged cellular components and induction of the enzyme flavin-containing monooxygenase 2. These results establish novel links between the pentose phosphate pathway, mitochondrial function, redox homeostasis, and organismal aging.