HuR controls mitochondrial morphology through the regulation of Bcl _xL translation

Abstract

Bcl _xL is a key prosurvival factor that in addition to controlling mitochondrial membrane permeability regulates mitochondrial network dynamics. The expression of Bcl _xL is regulated at the level of transcription, splicing and selective translation. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an anti-apoptotic cellular program, functions as a translational repressor of Bcl _xL. We show that HuR binds directly to the 5`UTR of Bcl _xL, and represses Bcl _xL translation through the inhibition of its internal ribosome entry site (IRES). Reduction of HuR levels leads to the derepression of Bcl _xL translation and subsequent rearrangement of the mitochondrial network. Our results place Bcl _xL into the HuR-regulated operon and provide further insight into the regulation of cellular stress response by HuR.