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Due to the hypoxic environment of chondrocytes and their heavy reliance on glycolysis, mitochondrial functions have long been considered of minimal relevance in these cells. However, as major suppliers of energy through the ATP they produce by OxPhos, mitochondria help to regulate the balance between anabolism and catabolism. In osteoarthritis (OA), the most prevalent joint disease, this balance is dysregulated. In addition, correlations between metabolic disorders and the risk of developing OA are also increasingly studied. In this context, mitochondrial dysfunctions in OA chondrocytes are emerging as a relevant area to propose efficient, yet unavailable, disease-modifying OA drugs (DMOADs). This narrative review examines the underlying mechanisms by which the mitochondrial functions become dysregulated in chondrocytes during OA. Drawing on up-to-date literature, it highlights how both structural and functional alterations of mitochondria contribute to OA pathology in chondrocytes. Finally, this review discusses the potential of mitochondria-targeted therapeutic strategies for OA, framed within a conceptual \u201c\n                    <jats:italic>repair<\/jats:italic>\n                    or\n                    <jats:italic>replace<\/jats:italic>\n                    \u201d approach.\n                  <\/jats:p>","DOI":"10.1038\/s41413-026-00548-y","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:54:47Z","timestamp":1780307687000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring mitochondrial functions and dysfunctions in chondrocytes: toward the identification of novel therapies for osteoarthritis"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2697-6663","authenticated-orcid":false,"given":"Lucie","family":"Danet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2754-3024","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Guicheux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-6902","authenticated-orcid":false,"given":"Marie-Astrid","family":"Boutet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6063-9901","authenticated-orcid":false,"given":"Claire","family":"Vinatier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"548_CR1","first-page":"230","volume":"59","author":"L Margulis","year":"1971","unstructured":"Margulis, L. 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