Journal article
Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak
LM Lindqvist, M Heinlein, DCS Huang, DL Vaux
Proceedings of the National Academy of Sciences of the United States of America | Published : 2014
Abstract
Antiapoptotic B-cell lymphoma 2 (Bcl-2) family members such as Bcl-2, myeloid cell leukemia 1 (Mcl-1), and B-cell lymphoma-X large (Bcl-xL) are proposed to inhibit autophagy by directly binding to the BH3 domain of Beclin 1/Atg6. However, these Bcl-2 family proteins also block the proapoptotic activity of Bcl-2-associated X (Bax) and Bcl-2 homologous antagonist/killer (Bak), and many inducers of autophagy also cause cell death. Therefore, when the mitochondrial-mediated apoptosis pathway is functional, interpretation of such experiments is complicated. To directly test the impact of the endogenous antiapoptotic Bcl-2 family members on autophagy in the absence of apoptosis, we inhibited their..
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NHMRC
Awarded by Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS)
Funding Acknowledgements
We thank Andreas Strasser for helpful discussions and H. Ierino for technical assistance. Funding for this project was provided by National Health and Medical Research Council (NHMRC) Grants 1016701 and 1020136. L. M. L. is a Bisby Fellow and holds an NHMRC Peter Doherty Early Career Fellowship (1035502) and a Canadian Institutes of Health Research (CIHR) Post-PhD Fellowship. NHMRC Research Fellowships are held by both D. C. S. H. (1043149) and D. L. V. (1020136). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS) Grant 361646.