PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila.

ABSTRACT: The mitochondrial unfolded protein response (UPR^mt) has been associated with long lifespan across metazoans. In Caenorhabditis elegans, mild developmental mitochondrial stress activates UPR^mt reporters and extends lifespan. We show that similar developmental stress is necessary and sufficient to extend Drosophila lifespan, and identify Phosphoglycerate Mutase 5 (PGAM5) as a mediator of this response. Developmental mitochondrial stress leads to activation of FoxO, via Apoptosis Signal-regulating Kinase 1 (ASK1) and Jun-N-terminal Kinase (JNK). This activation persists into adulthood and induces a select set of chaperones, many of which have been implicated in lifespan extension in flies. Persistent FoxO activation can be reversed by a high-protein diet in

SUBMITTER: Borch Jensen M 

PROVIDER: S-EPMC5614561 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature