Human Diseases and Mitochondrial Damage: Role of Cytochrome c – Cardiolipin Interaction as a Key Regulator of Cell Fate
- Pp. 56-79 (24)Roberto Santucci, Federica Sinibaldi and Laura Fiorucci
Apoptosis is a highly programmed cell death process that can be activated by various factors and is strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative or cardiovascular diseases. Mitochondria play a key role in the apoptotic process. The permeabilization of the outer mitochondrial membrane, occurring as mitochondrion is damaged, activates a series of events leading to cell death. Apoptosis is activated by various factors; among the various hypotheses formulated, the so-called ‘intrinsic’ pathway theory assumes that the process, which initiates in the mitochondrion, provokes the release of cytochrome c and other proapoptotic factors from the mitochondrial intermembrane space to cytosol. In the cytosol, cytochrome c exerts a pro-apoptotic action binding to the apoptosis protease activation factor (APAf-1) and forming a complex called ‘apoptosome’. The activation of procaspase 9 initiates an enzymatic reaction cascade leading to cell death. This review provides an overview of the key role played by mitochondria and cytochrome c in activating the apoptotic process.