title: A mitochondrial superoxide theory for oxidative stress diseases and aging.
abstract: Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA.
authors.forename: Hiroko P
authors.initials: HP
authors.lastname: Indo
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan.
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Yen
authors.affiliation: Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nakanishi
authors.affiliation: Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nagano
authors.affiliation: Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Invertebrates Zoology and Functional Morphology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremevskaya str., 17 Kazan 420-008, Russia ; Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science, ISS Science Project Office, Ibaraki 305-8505, Japan ; Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Oleg
authors.initials: O
authors.lastname: Gusev
authors.affiliation: Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Richard
authors.initials: R
authors.lastname: Cornette
authors.affiliation: Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 606-8522, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.affiliation: Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshishia University, Kyoto 610-0394, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Suenaga
authors.affiliation: Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Oki
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Oxidative Stress Research, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ozawa
authors.affiliation: Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40506, USA.
authors.forename: Daret K St
authors.initials: DK
authors.lastname: Clair
authors.affiliation: Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan ; Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Hideyuki J
authors.initials: HJ
authors.lastname: Majima
keywords: MnSOD; ROS; mitochondria; oxidative stress diseases and aging; superoxide theory
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