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Bcl-xL does not inhibit the function of Apaf-1
D D Newmeyer1, E Bossy-Wetzel, R M Kluck
1La Jolla Institute for Allergy and Immunology, 10355 Science Center Road, San Diego, CA 92121, USA.
Cell Death and Differentiation
|April 25, 2000
Summary
Bcl-xL protein inhibits cytochrome c release from mitochondria but does not block caspase-9 activation. This suggests Bcl-xL and Bcl-2 do not prevent apoptosome function, impacting apoptosis research.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Bcl-2 and Bcl-xL are key regulators of apoptosis, inhibiting cell death by controlling caspase activation.
- Two proposed mechanisms involve preventing cytochrome c release or directly inhibiting the apoptosome complex.
Purpose of the Study:
- To investigate whether Bcl-xL directly inhibits the function of the cytochrome c/Apaf-1/caspase-9 apoptosome.
Main Methods:
- Recombinant Bcl-xL protein was added to cell-free apoptotic systems from Jurkat cells and Xenopus eggs.
- Cytochrome c release and caspase activation were measured at varying Bcl-xL concentrations.
Main Results:
- Bcl-xL (50 nM) inhibited cytochrome c release from mitochondria.
- Despite associating with Apaf-1, Bcl-xL (1-5 microM) failed to inhibit caspase activation induced by exogenous cytochrome c.
Conclusions:
- Bcl-xL and Bcl-2 do not inhibit the apoptosome-mediated activation of caspase-9.
- These proteins primarily regulate apoptosis by controlling upstream events like cytochrome c release.