title: [Mechanisms and regulation of the programmed cell death].
abstract: The programmed cell death usually is identified with apoptosis, though a scheduled sequence of events can be observed also in autophagy, mitotic catastrophe and, under certain circumstances, in necrosis. Apoptosis begins with activation of the initiator caspases (cysteine proteases) in the signaling complexes: the apoptosome (on the intrinsic or mitochondrial pathway) or the degradosome (on the extrinsic or death receptor pathway). The proteolytic cascade then leads, through activation of downstream caspases and DNases, to digestion of cell components. Mitochondria play a central role in apoptosis by releasing cytochrome c--the essential component of the apoptosome, Smac/Diablo and OmiI/HtrA2--that bind the caspase inhibitors (IAPs), and endonuclease G and AIF--that are responsible for DNA degradation. Those factors get out of mitochondrium through the Bax and Bak protein-containing channels. The process is fast and complete, probably due to mechanoenzyme--driven remodeling of the organellum structure as well as to phospholipid peroxidation and proteolysis in the inner membrane. The release of the mitochondrial factors can be stimulated by protein p53, histone H1.2 and poly(ADP-ribose) that are sent from the nucleus in consequence of a cyto- and genotoxic stress, under the control of cAbl kinase.
authors.affiliation: Instytut Chemii i Techniki Jadrowej, Zakład Radiobiologii i Ochrony Zdrowia, ul. Dorodna 16, 03-950 Warszawa. iwonag@ichtj.waw.pl
authors.forename: Iwona
authors.initials: I
authors.lastname: Gradzka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases