Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation.

ABSTRACT:

Background

DNA damage such as double-stranded DNA breaks (DSBs) has been reported to stimulate mitochondrial biogenesis. However, the underlying mechanism is poorly understood. The major player in response to DSBs is ATM (ataxia telangiectasia mutated). Upon sensing DSBs, ATM is activated through autophosphorylation and phosphorylates a number of substrates for DNA repair, cell cycle regulation and apoptosis. ATM has been reported to phosphorylate the alpha subunit of AMP-activated protein kinase (AMPK), which senses AMP/ATP ratio in cells, and can be activated by upstream kinases. Here we provide evidence for a novel role of ATM in mitochondrial biogenesis through AMPK activation in response to etoposide-induced DNA damage.

Methodology/principal findings

Three pairs of huma

SUBMITTER: Fu X 

PROVIDER: S-EPMC2329593 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature