Integrated proteome and lipidome analyses place OCIAD1 at mitochondria-peroxisome intersection balancing lipid metabolism

OCIAD1 (Ovarian Cancer Immunoreactive Antigen Domain Containing 1) is a membrane protein largely localized to mitochondria, however, its function in health or disease is not well understood. To comprehensively characterize the molecular changes upon lack of OCIAD1, we used mass spectrometry to study the mitochondrial and cellular proteome and lipidome. We find extensive lipidome rearrangement in OCIAD1 KO cells, characterized by two main phenotypes of decreased ether phospholipids and decreased phospholipids with an odd number of carbons. The lipidomic changes suggest alterations in peroxisomal lipid metabolism. At the same time, proteins responsible for mitochondrial fatty acid β oxidation are significantly increased. Together with a global loss in peroxisomal proteins, aberrant peroxisomal morphology, and a meta-analysis of proximity labeling data, this gives a function to the previously observed partial localization of OCIAD1 to peroxisomes. We suggest a role for OCIAD1 in balancing mitochondrial and peroxisomal lipid metabolism, and a direct impact on the key enzymes FAR1 and ABCD3.