The mitochondrial death pathway: a promising therapeutic target in diseases
Gupta, Sanjeev Kass, George E.N. Szegezdi, Eva Joseph, Bertrand
Gupta, Sanjeev
Kass, George E.N.
Szegezdi, Eva
Joseph, Bertrand
Repository DOI
Publication Date
2009-07-01
Keywords
mitochondrial permeability transition, apoptosis, bcl-2, caspases, mitochondrial outer membrane permeabilization, permeability transition pore, cytochrome-c release, amyotrophic-lateral-sclerosis, adenine-nucleotide translocator, apoptosis-inducing factor, programmed cell-death, bcl-2 family-members, peripheral benzodiazepine-receptor, etoposide-induced apoptosis, electron-transport chain
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Article
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Citation
Gupta, Sanjeev; Kass, George E.N. Szegezdi, Eva; Joseph, Bertrand (2009). The mitochondrial death pathway: a promising therapeutic target in diseases. Journal of Cellular and Molecular Medicine 13 (6), 1004-1033
Abstract
The mitochondrial pathway to apoptosis is a major pathway of physiological cell death in vertebrates. The mitochondrial cell death pathway commences when apoptogenic molecules present between the outer and inner mitochondrial membranes are released into the cytosol by mitochondrial outer membrane permeabilization ( MOMP). BCL-2 family members are the sentinels of MOMP in the mitochondrial apoptotic pathway; the pro-apoptotic B cell lymphoma (BCL)-2 proteins, BCL-2 associated x protein and BCL-2 antagonist killer 1 induce MOMP whereas the anti-apoptotic BCL-2 proteins, BCL-2, BCL-x(L) and myeloid cell leukaemia 1 prevent MOMP from occurring. The release of pro-apoptotic factors such as cytochrome c from mitochondria leads to formation of a multimeric complex known as the apoptosome and initiates caspase activation cascades. These pathways are important for normal cellular homeostasis and play key roles in the pathogenesis of many diseases. In this review, we will provide a brief overview of the mitochondrial death pathway and focus on a selection of diseases whose pathogenesis involves the mitochondrial death pathway and we will examine the various pharmacological approaches that target this pathway.
Funder
Publisher
Wiley-Blackwell
Publisher DOI
10.1111/j.1582-4934.2009.00697.x
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland