{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:53:19Z","timestamp":1791190399413,"version":"4.1.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017534","name":"Inner Mongolia Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017534","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Osteoarthritis (OA) is a whole-joint disease characterized by metabolic reprogramming beyond structural degeneration. Increasing evidence indicates that lipid droplets (LDs) regulate lipid storage, mobilization and intracellular lipid routing, while alterations in mitochondrial metabolism determine the capacity of chondrocytes to adapt to metabolic stress. However, LD accumulation alone is insufficient to define metabolic dysfunction, as it may represent either adaptive buffering or maladaptive retention. This review proposes a lipid flux\u2013mitochondrial capacity matching framework to integrate lipid handling with mitochondrial oxidative capacity, redox regulation and quality control. We discuss how excessive lipid flux relative to mitochondrial capacity may promote oxidative stress, lipid peroxidation, ferroptosis, senescence and extracellular matrix disruption, whereas balanced lipid utilization supports chondrocyte homeostasis. Current evidence on LD biology, fatty acid oxidation, mitophagy and whole-joint metabolic communication is summarized, with clear distinction between direct OA evidence and findings from other cellular systems. Although organelle contact sites such as PLIN5\u2013FATP4, PLIN3\u2013VDAC3 and ESYT1\/2\u2013VAPB represent potential regulators of lipid routing, their functional relevance in OA chondrocytes remains to be established. Future studies integrating isotope tracing, metabolic flux analysis and dynamic organelle imaging are required to clarify how lipid routing and mitochondrial capacity jointly regulate OA progression.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1973436","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:15:25Z","timestamp":1791188125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid droplet\u2013mitochondria crosstalk in osteoarthritis: linking lipid routing to metabolic mismatch"],"prefix":"10.3389","volume":"13","author":[{"given":"Gang","family":"Meng","sequence":"first","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijie","family":"Hou","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Dong","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Chen","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hu","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Du","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanxi University of Traditional Chinese Medicine","place":["Jinzhong, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1038\/s41467-025-57405-5","article-title":"Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria-endoplasmic reticulum contact sites","volume":"16","author":"Bezawork-Geleta","year":"2025","journal-title":"Nat. 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