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Updated: May 22, 2026

Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
Mitochondrial Ca2+ uniporter (MCU) variants form plasma-membrane channels
Iuliia Polina1, Jyotsna Mishra2,3, Michael W Cypress1
1Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
None:
MCU, originally known as CCDC109A, is widely recognized as the gene responsible for encoding a pore-forming subunit of a Ca2+-selective channel, mitochondrial Ca2+ uniporter complex (mtCUC). While MCU expression is typically highly mitochondrial-specific, we report here a protein variant derived from the MCU gene, termed MCU-S, which lacks the mitochondria-targeting sequence (MTS) and forms a Ca2+-permeable channel outside of mitochondria. The mRNA of MCU-S was ubiquitously expressed in all cell types/tissues tested, with particularly high expression in human platelets. MCU-S protein formed Ca2+ channels at the plasma membrane, which exhibited similar channel properties to those observed in mtCUC. MCU-S channels at the plasma membrane served as an additional Ca2+ influx pathway for platelet activation. Our findings show that the MCU-S functions are completely distinct from the originally reported functions of the MCU gene and provide additional insights into the molecular importance of MCU variant-dependent cellular Ca2+ handling.
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