[Frontiers in Bioscience 14, 1197-1218, January 1, 2009]

[Frontiers in Bioscience 14, 1197-1218, January 1, 2009]

Crosstalk signaling between mitochondrial Ca²⁺ and ROS

Robert F. Feissner¹, Jolanta Skalska^1,2, Winston E. Gaum², Shey-Shing Sheu¹

1Mitochondrial Research and Innovation Group and Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, ²Department of Pediatrics, Division of Pediatric Cardiology, University of Rochester Medical Center, Rochester, NY 14642

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Mitochondrial Ca²⁺ dynamics: 3.1. Mitochondrial Ca²⁺ mobilization: uptake and efflux; 3.2. Ca²⁺ regulation of mitochondrial metabolism; 3.3. Ca²⁺ overload: the permeability transition and apoptosis
4. Ca²⁺ and mitochondrial reactive oxygen species (ROS): 4.1. Reactive oxygen species; 4.2. ROS defense mechanisms; 4.3. ROS production at complex I; 4.4. ROS production at complex III; 4.5. Other sources of mitochondrial ROS; 4.6. Does Ca²⁺ induce or decrease ROS production?
5. ROS and Ca²⁺ signaling: 5.1. Redox modulation of Ca²⁺ transporters
6. Crosstalk between Ca²⁺ and ROS signaling: 6.1. Mitochondrial Ca²⁺ microdomains; 6.2. Mitochondrial ROS microdomains; 6.3. Mitochondrial Ca²⁺ and ROS crosstalk
7. Perspectives
8. Acknowledgements
9. References

1. ABSTRACT

Mitochondria are central to energy metabolism as the source of much of the cell's ATP, as well as being a hub for cellular Ca²⁺ signaling. Mitochondrial Ca²⁺ is a positive effector of ATP synthesis, yet Ca²⁺ overload can lead to mitochondrial dysfunction and cell death. Moreover, Ca²⁺ uptake by mitochondria is involved in shaping cellular Ca²⁺ dynamics by regulating the concentrations of Ca²⁺ within microdomains between mitochondria and sarco/endoplasmic reticulum and plasma membrane Ca²⁺ transporters. Reactive oxygen species (ROS) generated as a consequence of ATP production in the mitochondria are important for cellular signaling, yet contribute to oxidative stress and cellular damage. ROS regulate the activity of redox sensitive enzymes and ion channels within the cell, including Ca²⁺ channels. For both Ca²⁺ and ROS, a delicate balance exists between the beneficial and detrimental effects on mitochondria. In this review we bring together current data on mitochondrial Ca²⁺ uptake, ROS generation, and redox modulation of Ca²⁺ transport proteins. We present a model for crosstalk between Ca²⁺ and ROS signaling pathways within mitochondrial microdomains.