Double-edged sword in cells: chemical biology studies of the vital role of cytochrome c in the intrinsic pre-apoptotic mitochondria leakage pathway

Abstract

Besides functioning as an electron transporter in the mitochondrial electron transport chain, cytochrome c (cyt c) is also one of the determinants in the execution of cell death. The interaction between cyt c and lipids has long been of great interest in biological systems, while the study of cyt c has attracted even more attention since its new function in apoptosis was discovered. Theories on the cause-effect signaling pathways have been proposed. However, until recently, some of the detailed parts have remained poorly understood in the big picture of cyt c-mediated apoptosis. In the past few years, new labelling, monitoring and detecting methods as well as in vitro model systems such as cyt c–cardiolipin (CL) or cyt c–membrane systems have been developed to overcome these drawbacks. The discovery of the versatile roles of cyt c in metabolic as well as apoptotic processes suggests cyt c per se as a potential drug target. In this review, we divide the whole cyt c-mediated pre-apoptotic mitochondrial leakage process into several sections in a chronological order and summarize the recent discoveries and hypotheses. With the combinatorial effort of modern interdisciplinary subjects such as chemical biology, bio-inorganic chemistry, structural biology and physical organic chemistry, we expect that researches in this field will shed light on our understanding of the whole intrinsic apoptotic process, and further contribute to health sciences.