Effect of cytochrome c on the generation and elimination of O2.- and H2O2 in mitochondria

Abstract

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 O2.- and H2O2 in mitochondria. The O2.- and H2O2 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 O2.- and H2O2 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 O2.- and H2O2 in mitochondria. Enough cytochrome c in the respiratory chain is needed for keeping O2.- and H2O2 at a lower physiological level. A dramatic increase of O2.- and H2O2 generation occurs when cytochrome c is released from the respiratory chain. The burst of O2.- and H2O2, 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.