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(Circulation Research. 2005;97:302.)
© 2005 American Heart Association, Inc.

Editorials

Mitochondria and Reactive Oxygen Species

An Evolution in Function

David D. Gutterman

From the Medical College of Wisconsin and VA Medical Center, Milwaukee.

Correspondence to Dr David D. Gutterman, Medical College of Wisconsin, Northwestern Mutual Professor of Cardiology, Senior Associate Dean for Research, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail dgutterm@mail.mcw.edu

See related article, pages 354–362

Key Words: potassium channel • vasodilation • calcium • mitochondria • oxidative stress

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Mitochondria are traditionally known as the energy generating centers of cells. Electron flux through the mitochondrial respiratory chain, an organized sequence of complex enzymes, hyperpolarizes the inner membrane, extruding newly generated ATP into the cytoplasm. An evolving paradigm shift has occurred in our understanding of mitochondrial function with the relatively recent observation that mitochondria are critical for the initiation of cellular apoptosis through release of cytochrome C.¹ Mitochondria are also responsible for generation of substantial amounts of superoxide caused by electron leakage from the oxidative phosphorylation pathway. Reactive oxygen species (ROS) generated from mitochondria have been implicated in various forms of cell signaling in the vasculature.²

Once thought to be a toxic byproduct of cellular metabolism, ROS including superoxide and hydrogen peroxide (H₂O₂) also participate in a large variety of vascular cell signaling processes including activation of eNOS³ and stimulation of cell growth and migration⁴ through modulation of intracellular calcium,⁵ and activation of transcription factors such as NF-B⁶ and protein kinases including ERK, p38MAPK, and Akt.^7,8 Thus, physiological levels of ROS may be responsible for regulation of vascular tone^9,10 and for stimulation of cell growth and migration.⁴

The discovery that mitochondrial function extends beyond ATP generation and that ROS may be key mediators of cellular physiology and pathology has opened new research vistas in vascular biology. Because mitochondria are responsible for the majority of ROS generated in most cells,¹¹ linking mitochondrial respiration with ROS effects on cellular function is logical. Indeed excess release of mitochondrial oxidants has . . . [Full Text of this Article]

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