@article{99365f113e6e46988f1d82b84e33bdbc,
title = "Mitochondrial Ca2+ uptake: Tortoise or hare?",
abstract = "Mitochondria are equipped with an efficient machinery for Ca2+ uptake and extrusion and are capable of storing large amounts of Ca2+. Furthermore, key steps of mitochondrial metabolism (ATP production) are Ca2+-dependent. In the field of cardiac physiology and pathophysiology, two main questions have dominated the thinking about mitochondrial function in the heart: 1) how does mitochondrial Ca2+ buffering shape cytosolic Ca2+ levels and affect excitation-contraction coupling, particularly the Ca2+ transient, on a beat-to-beat basis, and 2) how does mitochondrial Ca2+ homeostasis influence cardiac energy metabolism. To answer these questions, a thorough understanding of the kinetics of mitochondrial Ca2+ transport and buffer capacity is required. Here, we summarize the role of mitochondrial Ca2+ signaling in the heart, discuss the evidence either supporting or arguing against the idea that Ca2+ can be taken up rapidly by mitochondria during excitation-contraction coupling and highlight some interesting new areas for further investigation.",
keywords = "Ca transients, Calcium uniporter, Cellular energetics, Energy metabolism, Excitation-contraction coupling, Mitochondrial inner membrane, Sodium-calcium exchange",
author = "Brian O'Rourke and Blatter, {Lothar A.}",
note = "Funding Information: Dr. Brian O'Rourke is a Professor in the Division of Cardiology, Department of Medicine of the Johns Hopkins University. Dr. O'Rourke's laboratory uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states. A major emphasis of Dr. O'Rourke's work is to characterize the mechanisms of control and modulation of mitochondrial function. In this regard, he has elucidated how some ion channels in the mitochondrial inner membrane play an instrumental role in protecting myocytes from necrotic and apoptotic cell death (e.g., the mitochondrial K ATP and K Ca2+ channels), while others contribute to mitochondrial dysfunction (e.g., permeability transition pores and inner membrane anion channels). Over the course of his career, Dr. O'Rourke has been most interested in studying the dynamics of mitochondrial energetics by taking a cross-disciplinary approach, working with collaborators in the areas of computational biology, proteomics, biophysics and molecular biology to gain a comprehensive understanding of the integrative physiology of the cardiomyocyte. A main theme is to understand how failures at the subcellular level scale to produce global electrical and contractile dysfunction in the heart. Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms. Dr. O'Rourke currently directs a Program Project on mitochondrial function in cardiac disease (P01 HL081427), holds an NIH MERIT award (R37HL54598), and participates in a Systems Biology grant on sudden cardiac death (R33 HL087338).",
year = "2009",
month = jun,
doi = "10.1016/j.yjmcc.2008.12.011",
language = "English (US)",
volume = "46",
pages = "767--774",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "6",
}