[Frontiers in Bioscience 14, 4436-4443, January 1, 2009]

Mitochondrial nitric oxide synthase: current concepts and controversies

Zsombor Lacza1, Eszter Pankotai1, David W. Busija2

1Department of Human Physiology and Clinical Experimental Research, Semmelweis University, 1082 Budapest, Hungary, 2Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, U.S.A.

TABLE OF CONTENTS

1. abstract
2. Introduction
3. Discussion
3.1. Potential actions of NO in the mitochondria
3.2. The case for a genuine mitochondrial NOS
3.3. The case against a genuine mitochondrial NOS
3.4. Alternative sources of NO in the mitochondrion
4. Perspectives
5. Acknowledgements
6. References

1. ABSTRACT

New discoveries in the last decade significantly altered our view on mitochondria. They are no longer viewed as energy-making slaves but rather individual cells-within-the-cell. In particular, it has been suggested that many important cellular mechanisms involving specific enzymes and ion channels, such as nitric oxide synthase (NOS), ATP-dependent K+ (KATP) channels, and poly-(APD-ribose) polymerase (PARP), have a distinct, mitochondrial variant. Unfortunately, exploring these parallel systems in mitochondria have technical limitations and inappropriate methods often led to inconsistent results. For example, the intriguing possibility that mitochondria are significant sources of nitric oxide (NO) via a unique mitochondrial NOS variant has attracted intense interest among research groups because of the potential for NO to affect functioning of the electron transport chain. Nonetheless, conclusive evidence concerning the existence of mitochondrial NO synthesis is yet to be presented. This review summarizes the experimental evidence gathered over the last decade in this field and highlights new areas of research that reveal surprising dimensions of NO production and metabolism by mitochondria.