Progress in understanding mitochondrial calcium uniporter complex-mediated calcium signalling: A potential target for cancer treatment

Abstract

Due to its Ca 2+ buffering capacity, the mitochondrion is one of the most important intracellular organelles in regulating Ca 2+ dynamic oscillation. Mitochondrial calcium uniporter (MCU) is the primary mediator of Ca 2+ influx into mitochondria, manipulating cell energy metabolism, ROS production, and programmed cell death, all of which are critical for carcinogenesis. The understanding of the uniporter complex was significantly boosted by recent groundbreaking discoveries that identified the uniporter pore-forming subunit MCU and its regulatory molecules, including MCU-dominant negative β subunit (MCUb), essential MCU regulator (EMRE), MCU regulator 1 (MCUR1), mitochondrial calcium uptake (MICU) 1, MICU2, and MICU3. These provide the means and molecular platform to investigate MCU complex (uniplex)-mediated impaired Ca 2+ signalling in physiology and pathology. This review aims to summarize the progress of the understanding regulatory mechanisms of uniplex, roles of uniplex-mediated Ca 2+ signalling in cancer, and potential pharmacological inhibitors of MCU.