Transaldolase Inhibition Impairs Mitochondrial Respiration and Induces a Starvation-like Longevity Response in Caenorhabditis Elegans

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dc.contributor.authorWasko, Brian
dc.date.accessioned2020-10-16T17:05:25Z
dc.date.available2020-10-16T17:05:25Z
dc.date.issued2017
dc.description.abstractMitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanism exists 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 transaction 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.en_US
dc.identifier.citationBennett CF, Kwon JJ, Chen C, Russell J, Acosta K, Burnaevskiy N, et al. (2017) Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans. PLoS Genet 13(3): e1006695. https://doi.org/10.1371/journal.pgen.1006695en_US
dc.identifier.urihttps://hdl.handle.net/10657.1/2526
dc.publisherPMIDen_US
dc.subjectMitochondria, RNA interference, Aging, Caenorhabditis elegans, Gene expression, MAPK signaling cascades, Oxidation-reduction reactions, Oxidative stressen_US
dc.titleTransaldolase Inhibition Impairs Mitochondrial Respiration and Induces a Starvation-like Longevity Response in Caenorhabditis Elegansen_US
dc.typeArticleen_US

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