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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Apoptosis and Human Diseases: Mitochondrion Damage and Lethal Role of Released Cytochrome c as Proapoptotic Protein

Author(s): P. Caroppi, F. Sinibaldi, L. Fiorucci and R. Santucci

Volume 16 , Issue 31 , 2009

Page: [4058 - 4065] Pages: 8

DOI: 10.2174/092986709789378206

Price: $65


Apoptosis is strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative or cardiovascular diseases. It is a highly programmed cell death which can be activated by various factors. Mitochondria play a key role in the apoptotic process; their damage, which involves permeabilization of the outer mitochondrial membrane, activates a series of events that lead to cell death. Of the two proposed signaling pathways of apoptosis, i.e. the ‘extrinsic’ and the ‘intrinsic’ pathway, the latter is assumed to initiate in mitochondria. Its activation involves release of cytochrome c and other pro-apoptotic factors from the mitochondrial intermembrane space. In the cytosol, cytochrome c exerts its pro-apoptotic action. It binds to the apoptosis protease activation factor (APAf-1) and forms a complex indicated as ‘apoptosome’. The complex-induced activation of pro-caspase 9 initiates an enzymatic reaction cascade leading to the execution of apoptosis in cells. This review provides an overview of the key role played by mitochondria and cytochrome c in the activation of the apoptotic process.

Keywords: Apoptosis, mitochondria, mitochondrial membrane, cardiolipin, cytochrome c

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