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

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Abstract:

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; cardiolipin; cytochrome c; mitochondria; mitochondrial membrane

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709789378206

Affiliations: Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita di Roma “Tor Vergata”, Via Montpellier 1, 00133 Roma, Italy.

Publication date: November 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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