Control mechanisms of neuronal death

• Research unit: EU RFP
• Project number: 96.0067-2

Key words (English)

Neurons; apoptosis; Bax; Bid; Bcl-2; mitochondria cytochrome C; caspases

Alternative project number (English)

EU project number: BIO4CT960649

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Short description (English)

See abstract

Further information (English)

Full name of research-institution/enterprise:
Serono International SA
Serono Pharmaceutical Research Institute

Partners and International Organizations (English)

Drs Galli, Clarke, Mariani, Thompson, Navarette

Abstract (English)

We have shown that during apoptosis, Bax, which is normally cytosolic or loosely attached to mitochondria, becomes tighly inserted into the mitochondrial membranes. Treatment of mitochondria with sodium carbonate at an alcaline pH allows to distinguish two states of Bax : attached vs inserted. Moreover, digitonin treatment of mitochondria revealed that the insertion of Bax is in the outer mitochondrial membrane. Insertion of Bax follows its activation by Bid or by other proapoptotic members of the Bcl-2 family, in particular 'BH3-only' proteins. Thus, we found that it was possible to trigger Bax insertion by just adding Bid to Bax-containing mitochondria isolated from healthy cells. We also performed cross linking experiments to test whether other proteins were interacting with Bax in the outer mitochondrial membrane. We observed the formation of Bax oligomers and the presence of Bax immunoreactive bands which suggest that in addition to oligomerize, Bax forms a large complex with other mitochondrial proteins. None of the Bax-containing bands were found to be immunoreactive for VDAC and ANT, two proteins which have been reported previously to interact with Bax.
Eskes et al. (2000) Mol.Cell. Biol 20:929-935

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 96.0067-2