Whole genome siRNA cell-based screen links mitochondria to Akt signaling network through uncoupling of electron transport chain.

ABSTRACT: Forkhead transcription factors (FOXOs) alter a diverse array of cellular processes including the cell cycle, oxidative stress resistance, and aging. Insulin/Akt activation directs phosphorylation and cytoplasmic sequestration of FOXO away from its target genes and serves as an endpoint of a complex signaling network. Using a human genome small interfering RNA (siRNA) library in a cell-based assay, we identified an extensive network of proteins involved in nuclear export, focal adhesion, and mitochondrial respiration not previously implicated in FOXO localization. Furthermore, a detailed examination of mitochondrial factors revealed that loss of uncoupling protein 5 (UCP5) modifies the energy balance and increases free radicals through up-regulation of uncoupling protein 3 (UCP3). The incre

SUBMITTER: Senapedis WT 

PROVIDER: S-EPMC3093329 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature