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Pharmacology of Mitochondria pp 129–156Cite as

The Mitochondrial Ca2+ Uniporter: Structure, Function, and Pharmacology

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 240))

Abstract

Mitochondrial Ca2+ uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca2+ uptake and our current understanding of mitochondrial Ca2+ homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca2+ uniporter complex.

Jyotsna Mishra and Bong Sook Jhun contributed equally to this work.

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Abbreviations

[Ca2+]c :

Cytosolic Ca2+ concentrations

[Ca2+]m :

Mitochondrial Ca2+ concentrations

[Ca2+]o :

Extramitochondrial free Ca2+ concentrations

ATP:

Adenosine triphosphate

CaMK:

Ca2+/calmodulin kinase

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

CoQ10:

Coenzyme Q 10

CREB:

Cyclic adenosine monophosphate response element–binding protein

EMRE:

Essential MCU regulator

ER/SR:

Endoplasmic reticulum/Sarcoplasmic reticulum

ICDH:

Isocitrate dehydrogenase

IMM:

Inner mitochondrial membrane

IMS:

Intermembrane space

IP3R:

Inositol 1,4,5-trisphosphate receptor

LETM1:

Leucine zipper-EF-hand containing transmembrane protein 1

MAPK:

Mitogen-activated protein kinase

MCU:

Mitochondrial Ca2+ uniporter pore

MCUR1:

Mitochondrial Ca2+ uniporter regulator 1

MICU1:

Mitochondrial Ca2+ uptake 1

MICU2:

Mitochondrial Ca2+ uptake 2

MICU3:

Mitochondrial Ca2+ uptake 3

mPTP:

Mitochondrial permeability transition pore

mRyR1:

Mitochondrial ryanodine receptor 1

mtCU:

Mitochondrial Ca2+ uniporter

NMR:

Nuclear magnetic resonance

Npas4:

Neuronal PAS Domain Protein 4

OGDH:

α-Ketoglutarate/oxoglutarate dehydrogenase

OMM:

Outer mitochondrial membrane

PDH:

Pyruvate dehydrogenase

Pyk2:

Proline-rich tyrosine kinase 2

RaM:

Rapid mode of uptake

ROS:

Reactive Oxygen Species

Ru360:

Ruthenium 360

RyR:

Ryanodine receptor

TASK-3:

TWIK-related Acid-sensitive K+ channel

TRPC3:

Transient receptor potential channel 3

TRPV:

Transient Receptor Potential Vanilloid

VDAC:

Voltage dependent anion channel

α1-AR:

α1-Adrenoceptor

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Acknowledgments

This work was partly supported by National Heart, Lung, and Blood Institute Grants 2R01 HL-093671 and HL-114760 (to S. S. Sheu), 1R01 HL-122124 (to G. Csordas and S. S. Sheu). American Heart Association Grant 16SDG27260248 (to J. O-Uchi).

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  1. Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, 1020 Locust Street, Suite 543D, Philadelphia, PA, 19107, USA

    Jyotsna Mishra, Stephen Hurst & Shey-Shing Sheu

  2. Cardiovascular Research Center, Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA

    Bong Sook Jhun & Jin O-Uchi

  3. MitoCare Center for Mitochondrial Imaging Research and Diagnostics, Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    György Csordás

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  1. Jyotsna Mishra
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  2. Bong Sook Jhun
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  3. Stephen Hurst
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  4. Jin O-Uchi
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Correspondence to Jin O-Uchi , György Csordás or Shey-Shing Sheu .

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  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Harpreet Singh

  2. Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Shey-Shing Sheu

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Mishra, J., Jhun, B.S., Hurst, S., O-Uchi, J., Csordás, G., Sheu, SS. (2017). The Mitochondrial Ca2+ Uniporter: Structure, Function, and Pharmacology. In: Singh, H., Sheu, SS. (eds) Pharmacology of Mitochondria. Handbook of Experimental Pharmacology, vol 240. Springer, Cham. https://doi.org/10.1007/164_2017_1

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