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Autophagy. 2010 Nov;6(8):1032-41. doi: 10.4161/auto.6.8.13336.

Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.

Author information

1
Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, and College of Life Sciences, Peking University; Beijing, China.

Abstract

Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.

PMID:
20818185
DOI:
10.4161/auto.6.8.13336
[Indexed for MEDLINE]

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