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Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy\u2010induced endothelial dysfunction is still unclear. Here, in Hcy\u2010treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin\u2010related protein 1 (Drp1) and phosphate\u2010Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2\u00a0was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria\u2010associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5\u2010triphosphate receptor (IP3R)\u2013glucose\u2010regulated protein 75 (Grp75)\u2013voltage\u2010dependent anion channel\u00a0(VDAC)\u00a0complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy\u2010treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co\u2010treatment. In conclusion, Hcy\u2010induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R\u2013Grp75\u2013VDAC complex in MAMs.<\/jats:p>","DOI":"10.1002\/jbt.22737","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T07:55:57Z","timestamp":1615362957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Homocysteine induced a calcium\u2010mediated disruption of mitochondrial function and dynamics in endothelial cells"],"prefix":"10.1002","volume":"35","author":[{"given":"Li\u2010ting","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology Zhejiang University  Hangzhou 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