{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:36:33Z","timestamp":1779881793433,"version":"3.53.1"},"reference-count":69,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["138239"],"award-info":[{"award-number":["138239"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["141435"],"award-info":[{"award-number":["141435"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Isolated complex I deficiency (ICD) is commonly associated with mitochondrial diseases and closely mimics subacute necrotising encephalomyelopathy. This disorder is characterised by metabolic perturbations that affect energy metabolism pathways, including fatty acid metabolism. Here, we examined the tissue\u2010specific changes in fatty acid metabolism in the\n                    <jats:italic>Ndufs4<\/jats:italic>\n                    KO mice by employing mass\u2010spectrometry\u2010based proteomics as a hypothesis\u2010generating approach. We investigated proteomic changes in six tissues, including brain regions (brainstem, cerebellum, olfactory bulb), heart, kidney and liver, focusing on proteins involved in fatty acid metabolism. Although it is expected that most tissues, except for the brain, will utilise fatty acids as alternative energy sources when oxidative phosphorylation (OXPHOS) is deficient, our data revealed a more complex response. In the liver, fatty acid consumption (oxidation) was favoured as expected, but in the heart, fatty acid synthesis was favoured. In the kidney, proteins involved in almost all fatty acid metabolic processes (oxidation and synthesis) were downregulated. Our data demonstrate that metabolic adaptations in fatty acid metabolism to ICD were tissue\u2010specific and often in opposing directions. Understanding the differential adaptations across tissues could inform future treatment targets for mitochondrial disorders.\n                  <\/jats:p>","DOI":"10.1002\/pmic.13969","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T22:26:00Z","timestamp":1748816760000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tissue\u2010Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2143-3836","authenticated-orcid":false,"given":"Sibonelo Glen","family":"Khumalo","sequence":"first","affiliation":[{"name":"Mitochondria Research Group Biomedical and Molecular Metabolism Research (BioMMet) North\u2010West University Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie Zander","family":"Lindeque","sequence":"additional","affiliation":[{"name":"Mitochondria Research Group Biomedical and Molecular Metabolism Research (BioMMet) North\u2010West University Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Venter","sequence":"additional","affiliation":[{"name":"Mitochondria Research Group Biomedical and Molecular Metabolism Research (BioMMet) North\u2010West University Potchefstroom South 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