Review Mitochondrial apoptotic pathways

Apoptosis or programmed cell death (PCD) is a physiological process characteristic of pluricellular organisms leading to self-destruction of the cell. It is therefore involved in development, homeostasis and host defense. However, a significant difference has been shown between mammalian cell apoptosis and non-mammalian cell apoptosis: mitochondria are implicated only in the former. Execution of PCD includes the release of several proapoptotic proteins from the intermembrane space of mitochondria. They could exert their actions through a caspase dependent as well as a caspase independent way. On the other hand, regulation of PCD is mainly given by the Bcl-2 family members, which are in turn essentially regulated by activation of death receptors and/or DNA damage. Nowadays, execution of apoptosis is better known than its regulation. Nevertheless, we are still far of a complete understanding of the apoptotic process. Abbreviations: ADP, Adenosine diphosphate; AIF, Apoptosis-Inducing Factor; Akt, homologues of the v-akt oncogene; ANT, Adenine Nucleotide Translocator; Apaf-1, Apoptosis protease-activating factor-1; ATP, Adenosine triphosphate; Bad, Bak, Bax, Bid, Bim, Members of the Bcl-2 family; Bcl-2, B cell lymphoma-2 protein; BH, Bcl-2 homologue; DIABLO, Direct IAP binding Protein with low pI; DNA, deoxiribonucleic acid; FADD, Fas-associated death domain protein; Fas, receptor of death that belongs to the TNF receptor (TNFR) family; Fas-L, Fas ligand; HSPs, Heat Shock Proteins; HtrA, High-temperature requirement; IAP, Inhibitor of Apoptosis Protein; IMM, Inner Mitochondrial Membrane; IMS, Intermembrane Space; MA, Mitochondrial Anchorage; Noxa, p53-inducible (BH3)-only protein; Omi/HtrA 2 , mammalian serine protease; OMM, Outer Mitochondrial Membrane; PCD, Programmed Cell Death; PTP, Permeability Transition Pore; Puma, p53inducible (BH3)-only protein; ROS, Reactive Oxigen Species; SMAC, Second Mitochondrial Activator of Caspase; TNF-a, Tumor Necrosis Factor alpha; TNF-R, Tumor Necrosis Factor Receptor; TRADD, TNF-receptor-1 associated death domain protein; VDAC, Voltage-Dependent Anion Channel. BIOCELL 2005, 29(2): 149-161 ISSN 0327 9545 PRINTED IN ARGENTINA