Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy

Sophie Pattingre, Amina Tassa, Xueping Qu, Rita Garuti, Huan Liang Xiao, Noboru Mizushima, Milton Packer, Michael D. Schneider, Beth Levine

Research output: Contribution to journalArticlepeer-review

2542 Scopus citations

Abstract

Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. The anti-apoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is known about the functional significance of this interaction. Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death.

Original languageEnglish (US)
Pages (from-to)927-939
Number of pages13
JournalCell
Volume122
Issue number6
DOIs
StatePublished - Sep 23 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy'. Together they form a unique fingerprint.

Cite this