A mitochondrial superoxide theory for oxidative stress diseases and aging

Hiroko P. Indo; Hsiu-Chuan Yen; Ikuo Nakanishi; Ken-ichiro Matsumoto; Masato Tamura; Yumiko Nagano; Hirofumi Matsui; Oleg Gusev; Richard Cornette; Takashi Okuda; Yukiko Minamiyama; Hiroshi Ichikawa; Shigeaki Suenaga; Misato Oki; Tsuyoshi Sato; Toshihiko Ozawa; Daret K. St. Clair; Hideyuki J. Majima

doi:10.3164/jcbn.14-42

Review

A mitochondrial superoxide theory for oxidative stress diseases and aging

Hiroko P. Indo, Hsiu-Chuan Yen, Ikuo Nakanishi, Ken-ichiro Matsumoto, Masato Tamura, Yumiko Nagano, Hirofumi Matsui, Oleg Gusev, Richard Cornette, Takashi Okuda, Yukiko Minamiyama, Hiroshi Ichikawa, Shigeaki Suenaga, Misato Oki, Tsuyoshi Sato, Toshihiko Ozawa, Daret K. St. Clair, Hideyuki J. Majima

Author information

Hiroko P. Indo
Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences
Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine
Hsiu-Chuan Yen
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University
Ikuo Nakanishi
Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
Ken-ichiro Matsumoto
Radio-Redox-Response Research Team, Advanced Particle Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
Masato Tamura
Division of Gastroenterology, Faculty of Medicine, University of Tsukuba
Yumiko Nagano
Division of Gastroenterology, Faculty of Medicine, University of Tsukuba
Hirofumi Matsui
Division of Gastroenterology, Faculty of Medicine, University of Tsukuba
Oleg Gusev
Department of Invertebrates Zoology and Functional Morphology, Institute of Fundamental Medicine and Biology, Kazan Federal University
Japan Aerospace Exploration Agency, Institute of Space and Astronautical Science, ISS Science Project Office
Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences
Richard Cornette
Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences
Takashi Okuda
Anhydrobiosis Research Unit, National Institute of Agrobiological Sciences
Yukiko Minamiyama
Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University
Hiroshi Ichikawa
Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshishia University
Shigeaki Suenaga
Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences
Misato Oki
Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
Tsuyoshi Sato
Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences
Toshihiko Ozawa
Division of Oxidative Stress Research, Showa Pharmaceutical University
Daret K. St. Clair
Graduate Center of Toxicology and Markey Cancer Center, University of Kentucky College of Medicine
Hideyuki J. Majima
Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences
Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences

Keywords: superoxide theory, MnSOD, mitochondria, ROS, oxidative stress diseases and aging

JOURNAL FREE ACCESS

2015 Volume 56 Issue 1 Pages 1-7

DOI https://doi.org/10.3164/jcbn.14-42

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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.

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