PGAM5 interacts with Bcl-rambo and regulates apoptosis and mitophagy

Bcl-rambo, also known as BCL2L13, has been reported to regulate apoptosis, mitochondrial fragmentation, and mitophagy. However, the molecular mechanisms by which Bcl-rambo regulates these processes currently remain unclear. In the present study, we identified phosphoglycerate mutase member 5 (PGAM5) as an emerging partner interacting with Bcl-rambo through phenotypic Drosophila screening. The rough eye phenotype induced by human Bcl-rambo was partly rescued by the knockdown of pgam5-2, a mammalian ortholog of PGAM5. Bcl-rambo bound to PGAM5, and their interaction required the Bcl-rambo transmembrane domain. The co-expression of Bcl-rambo and PGAM5 promoted effector caspase activity in human embryonic kidney 293T cells. The transient overexpression of Bcl-rambo increased LC3B-II levels, which had been decreased by the co-expression of PGAM5. These results suggest that PGAM5 promotes Bcl-rambo-dependent apoptosis, but conversely interferes with Bcl-rambo-dependent mitophagy. •PGAM5 was identified as an emerging partner interacting genetically with Bcl-rambo.•PGAM5 bound physically with Bcl-rambo.•PGAM5 promoted Bcl-rambo-dependent caspase activity.•PGAM5 attenuated Bcl-rambo-induced increases in LC3B-II levels.•PGAM5 regulates Bcl-rambo activity for the initiation of apoptosis and mitophagy.