Effect of cytochrome c on the generation and elimination of O2*- and H2O2 in mitochondria.
The primary recognized function of cytochrome c is to act as an electron carrier transferring electrons from complex III to complex IV in the respiratory chain of mitochondria. Recent studies on cell apoptosis reveal that cytochrome c is responsible for the programmed cell death when it is released from mitochondria to cytoplasm. In this study we present evidence showing that cytochrome c plays an antioxidative role by acting on the generation and elimination of O(2)(*) and H(2)O(2) in mitochondria. The O(2)(*) and H(2)O(2) generation in cytochrome c-depleted Keilin-Hartree heart muscle preparation (HMP) is 7-8 times higher than that in normal HMP. The reconstitution of cytochrome c to the cytochrome c-depleted HMP causes the O(2)(*) and H(2)O(2) generation to exponentially decrease. An alternative electron-leak pathway of the respiratory chain is suggested to explain how cytochrome c affects on the generation and elimination of O(2)(*) and H(2)O(2) in mitochondria. Enough cytochrome c in the respiratory chain is needed for keeping O(2)(*) and H(2)O(2) at a lower physiological level. A dramatic increase of O(2)(*) and H(2)O(2) generation occurs when cytochrome c is released from the respiratory chain. The burst of O(2)(*) and H(2)O(2), which happens at the same time as cytochrome c release from the respiratory chain, should have some role in the early stage of cell apoptosis.
Zhao
Yungang
Y
National Laboratory of Biomacromolecule, Center for Molecular Biology, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China.
Wang
Zhi-Bo
ZB
Xu
Jian-Xing
JX
D000818:Animals; D017209:Apoptosis; D002417:Cattle; D003574:Cytochrome c Group / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004579:Electron Transport; D004583:Electrons; D006418:Heme / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008163:Luminescent Measurements; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D011190:Potassium Cyanide / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013053:Spectrophotometry; D013997:Time Factors
D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D006418:Heme; D006861:Hydrogen Peroxide; D011190:Potassium Cyanide