1. Mitochondrial Ca 2+ uniporter (MCU) variants form plasma-membrane channels.
- Author
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Polina I, Mishra J, Cypress MW, Landherr M, Valkov N, Chaput I, Nieto B, Mende U, Zhang P, Jhun BS, and O-Uchi J
- Abstract
MCU is widely recognized as a responsible gene for encoding a pore-forming subunit of highly mitochondrial-specific and Ca
2+ -selective channel, mitochondrial Ca2+ uniporter complex (mtCUC). Here, we report a novel short variant derived from the MCU gene (termed MCU-S) which lacks mitochondria-targeted sequence and forms a Ca2+ - permeable channel outside of mitochondria. MCU-S was ubiquitously expressed in all cell-types/tissues, with particularly high expression in human platelets. MCU-S 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 finding is completely distinct from the originally reported MCU gene function and provides novel insights into the molecular basis of MCU variant-dependent cellular Ca2+ handling.- Published
- 2023
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