A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia/Reoxygenation Injury

作者：Joshua J. Woods, Neeharika Nemani, Santhanam Shanmughapriya, Akshay Kumar, MengQi Zhang, Sarah R. Nathan, Manfred Thomas, Edmund J. Carvalho, Ramachandran Karthik, Subramanya Srikantan, Peter B. Stathopulos, Justin J. Wilson, Muniswamy Madesh · 发表于：ACS Central Science · 年份：2019 · DOI：10.1021/acscentsci.8b00773 · 被引用次数：166 · 研究领域：Mitochondrial Function and Pathology、ATP Synthase and ATPases Research、RNA modifications and cancer

). Dose-dependent studies reveal that Ru265 is more potent than the currently employed MCU inhibitor Ru360. Site-directed mutagenesis of Cys97 in the N-terminal domain of human MCU ablates the inhibitory activity of Ru265, suggesting that this matrix-residing domain is its target site. Additionally, Ru265 prevented hypoxia/reoxygenation injury and subsequent mitochondrial dysfunction, demonstrating that this new inhibitor is a valuable tool for studying the functional role of the MCU in intact biological models.