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

Ovarian cancer immunoreactive antigen domain-containing 1 (OCIAD1) 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 show that there is extensive lipidome rearrangement in OCIAD1 knockout (KO) cells, characterized by two main phenotypes of decreased levels of ether phospholipids and decreased levels of 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.