Document Type

Article

Publication Date

5-20-2026

Comments

This article is the author’s final published version in Communications Biology, Volume 9, Issue 1, 2026, Article number 1074.

The published version is available at https://doi.org/10.1038/s42003-026-10285-x. Copyright © The Author(s) 2026.

 

Abstract

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

42162263

Language

English

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