The mitochondrial Ca2+ uniporter: Regulation by auxiliary subunits and signal transduction pathways

Bong Sook Jhun, Jyotsna Mishra, Sarah Monaco, Deming Fu, Wenmin Jiang, Shey Shing Sheu, Jin O-Uchi

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Mitochondrial Ca2+ homeostasis, the Ca2+ influx-efflux balance, is responsible for the control of numerous cellular functions, including energy metabolism, generation of reactive oxygen species, spatiotemporal dynamics of Ca2+ signaling, and cell growth and death. Recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter (MCU) provides new possibilities for application of genetic approaches to study the mitochondrial Ca2+ influx mechanism in various cell types and tissues. In addition, the subsequent discovery of various auxiliary subunits associated with MCU suggests that mitochondrial Ca2+ 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 Ca2+ uptake through mtCUC. These observations indicate that mtCUCs form a local signaling complex at the inner mitochondrial membrane that could significantly regulate mitochondrial Ca2+ handling, as well as numerous mitochondrial and cellular functions. In this review we discuss the current literature on mitochondrial Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)C67-C80
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1
StatePublished - Jul 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was partly supported by American Heart Association, AHA Grants 14BGIA18830032 and 16SDG27260248 (to J. O-Uchi), W. W. Smith Charitable Trust Medical Research Grant H1403 (to J. O-Uchi), and National Heart, Lung, and Blood Institute, NHGRI Grants 2R01 HL-093671 and 1R01 HL-122124 (to S. S. Sheu). J. O-Uchi is a recipient of 2015 New Investigator Award from American Physiological Society, Cell and Molecular Physiology Section.

Publisher Copyright:
© 2016 the American Physiological Society.


  • CCDC109A
  • Ca/calmodulin-dependent protein kinase II
  • MCUb
  • Phosphorylation
  • Proline-richtyrosine kinase 2


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