REVIEW: Mitochondrial Metabolism of Reactive Oxygen Species

---

A. Yu. Andreyev^1,2, Yu. E. Kushnareva^1,3, and A. A. Starkov^1,4*

¹Alumni of Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

²University of California, San Diego, La Jolla, California 92093, USA

³The Burnham Institute, Del E. Webb Center for Neuroscience and Aging, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA

⁴Weill Medical College Cornell University, 585 E. 68th St., New York, NY 10021, USA; E-mail: ans2024@med.cornell.edu

^* To whom correspondence should be addressed.

Received September 28, 2004

---

Oxidative stress is considered a major contributor to etiology of both “normal” senescence and severe pathologies with serious public health implications. Mitochondria generate reactive oxygen species (ROS) that are thought to augment intracellular oxidative stress. Mitochondria possess at least nine known sites that are capable of generating superoxide anion, a progenitor ROS. Mitochondria also possess numerous ROS defense systems that are much less studied. Studies of the last three decades shed light on many important mechanistic details of mitochondrial ROS production, but the bigger picture remains obscure. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal. An integrative, systemic approach is applied to analysis of mitochondrial ROS metabolism, which is now dissected into mitochondrial ROS production, mitochondrial ROS removal, and mitochondrial ROS emission. It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.

---

KEY WORDS: mitochondria, reactive oxygen species, superoxide, antioxidants, oxidative stress

---