{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:46:39Z","timestamp":1785923199704,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministero per l\u2019Universit\u00e0 e la Ricerca","award":["2017-20172T2MHH_002"],"award-info":[{"award-number":["2017-20172T2MHH_002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pathogenic variants of the mammalian optic atrophy 1 (OPA1) protein, a key regulator of mitochondrial fusion, may lead to severe mitochondrial dysfunction and morphological alterations, and have also been proposed to be involved in remodeling the mitochondrial membranes lipid profile. To address this last issue, a lipidomic workflow based on HILIC-ESI-HRMS was applied to profile major classes of mitochondrial membrane phospholipids (PL), namely phosphatidylcholines (PCs), -ethanolamines (PEs), and -inositols (PIs), along with cardiolipins (CLs), in mouse embryonic fibroblasts knocked out for Opa1 gene (Opa1\u2212\/\u2212 MEFs) and expressing human OPA1 isoform 1 (ISO1) or one of four well-known pathogenic variants (I382M, D603H, G439V and R445H). A total of 122 common sum compositions were recognized for PLs in the four classes across the five sample types. Chemometrics on the respective quantitative data indicated a lower prevalence of alk(en)yl\/acyl species (O-PCs and O-PEs) within the PC and PE classes, along with a higher relative contribution of highly unsaturated PI and CL species, when severely pathogenic R445H and G439V variants were expressed. In contrast, the I382M variant was associated with a greater relative contribution of less-unsaturated PI and CL species. These findings indicate that pathogenic OPA1 variants are associated with distinct mitochondrial phospholipid profiles, opening interesting perspectives for future direct experimental validation of an eventual relationship existing between OPA1 variants, inter-organelle phospholipid trafficking, and mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/molecules31152719","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"2719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipidomics Based on HILIC-ESI-HRMS Reveal Subtle Changes in the Mitochondrial Phospholipidome of Mouse Embryonic Fibroblasts Expressing Pathogenic Variants of Human OPA1 Protein"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-7168","authenticated-orcid":false,"given":"Andrea","family":"Castellaneta","sequence":"first","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0025-3350","authenticated-orcid":false,"given":"Ilario","family":"Losito","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Universit\u00e0 degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, Italy"},{"name":"Centro Interdipartimentale di Spettrometria di Massa per Ricerche Tecnologiche (SMART), Universit\u00e0 degli Studi di Bari Aldo Moro, Via Orabona 4, 70126 Bari, 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