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Updated: Dec 14, 2025

Author Spotlight: Unveiling Mitochondrial Contact Sites and Architectural Insights
Published on: June 16, 2023
Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2
Chongyuan Wang1, Agata Jacewicz1, Bryce D Delgado1,2
1Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
Abstract:
The mitochondrial calcium uniporter is a Ca2+-gated ion channel complex that controls mitochondrial Ca2+ entry and regulates cell metabolism. MCU and EMRE form the channel while Ca2+-dependent regulation is conferred by MICU1 and MICU2 through an enigmatic process. We present a cryo-EM structure of an MCU-EMRE-MICU1-MICU2 holocomplex comprising MCU and EMRE subunits from the beetle Tribolium castaneum in complex with a human MICU1-MICU2 heterodimer at 3.3 Å resolution. With analogy to how neuronal channels are blocked by protein toxins, a uniporter interaction domain on MICU1 binds to a channel receptor site comprising MCU and EMRE subunits to inhibit ion flow under resting Ca2+ conditions. A Ca2+-bound structure of MICU1-MICU2 at 3.1 Å resolution indicates how Ca2+-dependent changes enable dynamic response to cytosolic Ca2+ signals.
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