A trio has turned into a quartet: DJ-1 interacts with the IP3R-Grp75-VDAC complex to control ER-mitochondria interaction.

The outer mitochondrial membrane protein VDAC interacts with the ER protein IP3R via chaperone Grp75 to form a molecular complex that couples mitochondria to the ER and contributes to functional mitochondria-ER contacts (MERCs), essential for efficient calcium (Ca2+) transfer. A new study by Liu et al. identifies the PD protein DJ-1 as a component of the IP3R-Grp75-VDAC complex. DJ-1 ablation impairs mitochondria-ER association and Ca2+ crosstalk, and impacts the stability of the trio.