CYTOCHROME C –LIPID INTERACTION IN THE REGULATION OF CELL FATE: RESPIRATION, APOPTOSIS AND DISEASES

Cytochrome c (cyt c) functions as a mobile electron carrier in the respiratory chain anchored to the external side of the inner mitochondrial membrane and shuttling electrons from cyt c reductase to cyt c oxidase. A further function of cyt c, beyond respiration, is realized outside mitochondria in the apoptotic program. Cyt c may respond to different environments by changing its fold, thus favouring the exertion of different biological functions in different pathophysiological cell conditions. The binding of lipids (free fatty acids as well as acidic phospholipids) to cyt c induces conformational changes and partial unfolding of the protein, strongly influencing cyt c oxidase/peroxidase activity. In the early events of apoptosis, the interaction of cyt c with a mitochondrion-specific phospholipid, cardiolipin (CL), brings about a conformational transition of the protein and acquirement of peroxidase activity. Transitions among different conformations are regulated by endogenous molecules such as ATP. Apoptosis is strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative and cardiovascular diseases, and derangements of cardiolipin biosynthesis and remodeling are crucial in regulation of apoptosis. So as the role of cyt c in respiration and apoptosis rely on its interaction with CL, in the present book chapter we will review the structural features of this complex. Then we shall describe how perturbations in CL amount, acyl composition and CL-driven allosteric modulation of the cyt c properties, may contribute to cell fate.