Biological roles of Cytochrome c: mitochondrial electron transport, programmed cell death and gain of peroxidatic activity

Abstract

Cytochrome c (cyt c) is a small monomeric protein of 13.0 KDa, which is positively charged at physiological pH. It has an hexa-coordinated heme, being the His18 and Met80 the fifth and sixth coordination position, respectively. It is a soluble molecule that associates through electrostatic interactions to the outer side of the inner mitochondrial membrane where it plays an important role as an electron carrier between complexes III and IV of the mitochondrial respiratory chain, forming part of one of the main catabolic pathways to generate ATP. Furthermore, cyt c is involved in two other essential cell functions: apoptosis and membrane cardiolipin peroxidation. Cyt c peroxidase activity is essential for the initiation of apoptosis leading to the specific oxygenation of cardiolipin by the production of hydroperoxides of cardiolipin, which are required for the release of other pro-apoptotic factors. During apoptosis, cyt c is released from the intermembrane space of mitochondria into the cytosol, where it forms a complex with APAF-1 and ATP, triggering the caspase-dependent machinery. Summarizing, this function of cyt c is very important in programmed cell death. Thus, it is critical for the proper elimination of damaged cells with failing cellular processes, preventing the spread of debris. This monograph aims to gather information on these three main functions of cyt c, stressing their importance for cell life.