ACS Central Science · 2019 · 161 citations · 71 references
Life SciencesMedicinal ChemistryPharmacologyBioenergeticsCellular MetabolismMitochondrial BiologyMitochondrial BioenergeticsMitochondrial Calcium HomeostasisMitochondrial DysfunctionMitochondrial MetabolismMitochondrial PhysiologyMitochondrial SignalingCa2+ SignalingHypoxia-reoxygenation InjuryMitochondrial Calcium DynamicsMitochondrial Calcium HandlingMitochondrial Calcium Signaling PathwaysMitochondrial Calcium Uniporter ComplexMitochondrial Dysfunction TherapeuticsReoxygenation Effects
). 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.
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A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
Diego De Stefani, Anna Raffaello, Enrico Teardo et al. · Nature · 2011 · 1.9K citations · Full text