Nathan Brady: "Mechanisms and functional consequences of mitochondrial autophagy"

Nathan Brady
Systembiologie von Zelltod-Mechanismen, DKFZ Heidelberg

Mechanisms and functional consequences of mitochondrial autophagy

BH3-only proteins integrate apoptosis and autophagy pathways, yet the nature of these interactions and their functional consequences are not fully resolved. We have determined that the BH3-only protein Bnip3 induces autophagic degradation of mitochondria (mitophagy) via binding of its LC3-Interacting Region (LIR) to Atg8 proteins, in a manner dependent on serine phosphorylation at the LIR. Functionally, Bnip3-driven degradation of mitochondria limits cytochrome c release capacity. These results suggest a novel cell fate decision, whereby phosphorylation-controlled interactions of pro- and anti-apoptotic Bcl-2 members with Atg8 proteins determine either pro-death mitochondrial apoptosis signaling or pro-survival mitophagy.