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.

Keywords:
Mitochondrial biology, Peroxisomes, Proteomics, Lipidomics, Lipid metabolism
Subjects:
Biochemistry, Cell biology and disease, Lipid biology, Organelles

Author contributions

Conceptualization: V.L., M.D., B.W., A.C.; Data curation: V.L., M.C., K.K.; Formal analysis: V.L., M.C., K.K., M.R., D.S., M.S.; Funding acquisition: V.L., B.W., M.S.; Investigation: V.L., M.C., K.K., M.R., T.A.S., V.R.; Methodology: V.L., M.R., D.S., M.D.; Project administration: V.L., A.C.; Resources: V.L., M.D., A.C.; Software: V.L., M.C., K.K.; Supervision: V.L., M.D., A.C.; Validation: M.C., H.D., V.R.; Visualization: V.L., M.C., K.K., T.A.S., M.S.; Writing – original draft: V.L., A.C.; Writing – review & editing: V.L., M.C., M.R., V.R., D.S., M.D., M.S., A.C.

Funding

This work was supported by the National Science Centre, Poland (2021/40/C/NZ3/00283). V.L. was additionally supported by the Foundation for Polish Science (START 064.2022) and the European Molecular Biology Organization (ALTF 474-2021). A.C. is supported by the National Science Centre, Poland (2019/35/B/NZ3/04066). Research in the Warscheid lab was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; project ID 541758684/SPP 2453, GRK 2234/2, and the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 812968. M.S. is supported by grants from the Biotechnology and Biological Sciences Research Council (BB/W015420/1; BB/V018167/1). For the purpose of open access, the authors apply a Creative Commons Attribution (CC-BY) licence to any Author Accepted Manuscript version arising.

Data and resource availability

The mass spectrometry lipidomics data have been deposited to MetaboLights (Yurekten et al., 2024) with the dataset identifier MTBLS12329. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2025) partner repository with the dataset identifier PXD061576. Data analysis and visualization code is available at https://github.com/KacperKaszuba0608/OCIAD1-Analysis.

First Person

This article has an associated First Person interview with the first author of the paper.

Special Issue

This article is part of the Special Issue ‘Cell Biology of Mitochondria’, guest edited by Ana J. Garcia-Saez and Heidi McBride. See related articles at https://journals.biologists.com/jcs/issue/138/9.

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2025
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