Selective recognition of mitochondrial acyl carrier protein by the regulatory protein LYRM2.

Human mitochondrial fatty acid synthesis plays a central role in coordinating lipid metabolism with respiratory chain biogenesis through the central mitochondrial acyl carrier protein (mACP). Although several Leucine-Tyrosine-Arginine motif (LYRM) family mitochondrial regulatory proteins have been shown to associate with mACP, the structure or function of most of them has remained undefined. Here, we identify one of the regulatory proteins, LYRM2, as an acyl-chain selective mACP-binding protein. Systematic expression screening of underexplored regulatory proteins revealed LYRM2 as uniquely stable in isolation. Gel electrophoresis analysis demonstrated specific complex formation between LYRM2 and acylated mACP. Biophysical and analytical analyses showed preferential binding to long-chain acyl-mACP species, with strongest interactions observed for C12. These results establish LYRM2 as a selective mACP-interacting protein and support a role for acyl-state recognition in mitochondrial regulatory signaling.