Regulatory network analysis of endoplasmic reticulum–mitochondrial contacts

Abstract

The contact of subcellular organelles serves as molecular signaling hubs to maintain cellular homeostasis. Endoplasmic Reticulum‐Mitochondria Contacts (ERMC) are one of these signaling hubs. They regulate diverse cellular activities such as Ca 2+ or lipid exchange, and mitochondria dynamics including metabolism, apoptosis and autophagy. The significance of ERMCs has recently been highlighted its dysregulation is linked to metabolic disease and neurodegenerative diseases. We previously identified multiple physical components of ERMCs using engineered ascorbate peroxidase (APEX) to map the ERMCs proteome. The identified 405 proteins with a 2.0‐fold cut‐off ratio (log base 2) in culture (SILAC)‐LC/MS‐MS quantification are classified by gene set enrichment analysis (GSEA). The analysis shows protein biosynthesis‐related proteins are enriched along with several Rho/kinase proteins. To investigate ERMC regulatory network, we screened 1126 compounds and ORFs identified in the proteomic analysis with a Split‐Rluc8 complementation assay; a biosensor that measures ERMCs. We found several modulators of adrenergic signaling associated with increased ERMC. These results may be useful to elucidate the regulation of ERMCs, understand ERMC physiology and unravel the disease mechanism. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .