Mitochondrial generation of reactive oxygen species and its role in aerobic life.
Mitochondria are the major site for the generation of ATP at the expense of molecular oxygen. Significant fractions (approximately 2%) of oxygen are converted to the superoxide radical and its reactive metabolites (ROS) in and around mitochondria. Although ROS have been known to impair a wide variety of biological molecules including lipids, proteins and DNA, thereby causing various diseases, they also play critical roles in the maintenance of aerobic life. Because mitochondria are the major site of free radical generation, they are highly enriched with antioxidants including GSH and enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase, on both sides of their membranes to minimize oxidative stress in and around this organelle. The present work reviews the sites and mechanism of ROS generation by mitochondria, mitochondrial localization of Mn-SOD and Cu,Zn-SOD which has been postulated for a long time to be a cytosolic enzyme. The present work also describes that a cross-talk of molecular oxygen, nitric oxide (NO) and superoxide radicals regulates the circulation, energy metabolism, apoptosis, and functions as a major defense system against pathogens. Pathophysiological significance of ROS generation by mitochondria in the etiology of aging, cancer and degenerative neuronal diseases is also described.
Inoue
Masayasu
M
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan. inoue@med.osaka-cu.ac.jp
Sato
Eisuke F
EF
Nishikawa
Manabu
M
Park
Ah-Mee
AM
Kira
Yukimi
Y
Imada
Isuke
I
Utsumi
Kozo
K
D000332:Aerobiosis / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001775:Blood Circulation / Q000502:physiology; D002331:Carnitine / Q000494:pharmacology; D002945:Cisplatin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004272:DNA, Mitochondrial / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D002945:Cisplatin; D002331:Carnitine; D010100:Oxygen