Abstract MCU , originally known as CCDC109A , is widely recognized as the gene responsible for encoding a pore-forming subunit of a Ca 2+ -selective channel, mitochondrial Ca 2+ 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 Ca 2+ -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 Ca 2+ 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 Ca 2+ 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 Ca 2+ handling.
Polina et al. (Wed,) studied this question.