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- Title
Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.
- Authors
Bennett, Christopher F.; Kwon, Jane J.; Chen, Christine; Russell, Joshua; Acosta, Kathlyn; Burnaevskiy, Nikolay; Crane, Matthew M.; Bitto, Alessandro; Vander Wende, Helen; Simko, Marissa; Pineda, Victor; Rossner, Ryan; Wasko, Brian M.; Choi, Haeri; Chen, Shiwen; Park, Shirley; Jafari, Gholamali; Sands, Bryan; Perez Olsen, Carissa; Mendenhall, Alexander R.
- Abstract
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.
- Subjects
MITOCHONDRIA; OXIDATIVE stress; CAENORHABDITIS elegans; PENTOSE phosphate pathway; TRANSALDOLASE
- Publication
PLoS Genetics, 2017, Vol 13, Issue 3, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1006695