The mitochondrial Ca 2+ uniporter: regulation by auxiliary subunits and signal transduction pathways

• Published in: American Journal of Physiology: Cell Physiology 2016-07, Vol.311 (1), p.C67-C80
• Main Authors: Jhun, Bong Sook, Mishra, Jyotsna, Monaco, Sarah, Fu, Deming, Jiang, Wenmin, Sheu, Shey-Shing, O-Uchi, Jin
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00319.2015

Mitochondrial Ca 2+ homeostasis, the Ca 2+ influx-efflux balance, is responsible for the control of numerous cellular functions, including energy metabolism, generation of reactive oxygen species, spatiotemporal dynamics of Ca 2+ signaling, and cell growth and death. Recent discovery of the molecular identity of the mitochondrial Ca 2+ uniporter (MCU) provides new possibilities for application of genetic approaches to study the mitochondrial Ca 2+ influx mechanism in various cell types and tissues. In addition, the subsequent discovery of various auxiliary subunits associated with MCU suggests that mitochondrial Ca 2+ uptake is not solely regulated by a single protein (MCU), but likely by a macromolecular protein complex, referred to as the MCU-protein complex (mtCUC). Moreover, recent reports have shown the potential role of MCU posttranslational modifications in the regulation of mitochondrial Ca 2+ uptake through mtCUC. These observations indicate that mtCUCs form a local signaling complex at the inner mitochondrial membrane that could significantly regulate mitochondrial Ca 2+ handling, as well as numerous mitochondrial and cellular functions. In this review we discuss the current literature on mitochondrial Ca 2+ uptake mechanisms, with a particular focus on the structure and function of mtCUC, as well as its regulation by signal transduction pathways, highlighting current controversies and discrepancies.