Science China Life Sciences

, Volume 54, Issue 8, pp 763–769

Distinctive characteristics and functions of multiple mitochondrial Ca2+ influx mechanisms

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DOI: 10.1007/s11427-011-4203-9

Cite this article as:
Pan, S., Ryu, SY. & Sheu, SS. Sci. China Life Sci. (2011) 54: 763. doi:10.1007/s11427-011-4203-9


Intracellular Ca2+ is vital for cell physiology. Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure, neuron-degeneration, and diabetes. To ensure an effective intracellular Ca2+ dynamics, various Ca2+ transport proteins localized in different cellular regions have to work in coordination. The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains. Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago, extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane. The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter (MCU). The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx. Since multiple Ca2+ influx mechanisms (e.g. L-, T-, and N-type Ca2+ channel) have their unique functions in the plasma membrane, it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types. During the last decade, four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified. These are mitochondrial ryanodine receptor, mitochondrial uncoupling proteins, LETM1 (Ca2+/H+ exchanger), and MCU and its Ca2+ sensing regulatory subunit MICU1. Here, we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics, Ca2+ dependence, and pharmacological characteristics. Their potential physiological and pathological implications are also discussed.


mitochondrial calcium channelscalcium transportmitochondriaheartryanodine receptor
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© The Author(s) 2011

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Center for Translational Medicine, Department of MedicineThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of PhysiologySeoul National University College of MedicineSeoulRepublic of Korea