The European Cell Death Organisation (ECDO), with the support of the EU-Marie Curie Actions, organized the 12th Euroconference on Apoptosis in Chania, Greece, from 17 to 20 September 2004. The meeting, which was held in the ‘Arsenali’ conference centre, a recently restored Venetian building situated in the picturesque old harbour of Chania, was attended by 310 participants from all continents. For the first time, the Euroconference was combined with a training course, aiming to familiarize young scientists and newcomers to the field with some of the basic concepts, methodologies, and tools used in the study of programmed cell death. Thus, the first training course on ‘Concepts and Methods in Programmed Cell Death’, to which most of the first day was dedicated, consisted of seven 1-h presentations focused on the mechanisms behind programmed cell death and the apoptotic responses (R Lockshin, G Salvesen, P Krammer, W Bursch), as well as the technological approaches that can be employed in their study (P Bernardi, E Golemis, P Silver). Details on the presentations can be found on the conference web-site, http://ecdo.maich.gr.
In his keynote lecture, Boris Zhivotovsky focused on the interplay between nuclei and mitochondria and the nature of the signals travelling between them during the apoptotic process. Caspase-2 is unique among caspases in that it has nuclear localization and different cleavage specificity (requiring the pentapeptide VDVED). Upon DNA damage, cleavage of the pentapeptide occurs earlier than activation of other caspases, while inhibition of procaspase-2 inhibits cyt c release, annexin externalization, and DNA fragmentation. Expression of p53 was shown to be important for caspase-2 activation. Incubation of permeabilized Jurkat cells with recombinant caspase-2 induces the release of cyt c, suggesting a direct action of caspase-2 on the mitochondria, which cannot be rescued by overexpression of Bcl-2. No other caspase could effect cyt c release in cells or cell extracts, and apoptosis inducing factor (AIF) was only released subsequent to mitochondrial permeability transition. Moreover, processed caspase-2 could still release cyt c in permeabilized Bax/Bak double-knockout MEFs. Proteolytic activity was not required for this effect and experiments with liposomes indicated that processed caspase-2 could be competing with cardiolipin for cyt c release. On a different note, in non-small lung cancer cells (NSCLC), which are resistant to DNA damage-induced apoptosis, cyt c was released but no active caspase-3 translocated to the nucleus. Staurosporin could still induce cell death by causing the release and migration of AIF to the nucleus. Blocking AIF migration also blocked staurosporin-induced cell death, indicating that a real dialogue exists between the organelles for both signalling and execution of cell death.
