HuR controls mitochondrial morphology through the regulation of Bcl(xL) translation

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.