We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes.
- Authors
Shimizu, Shigeomi; Kanaseki, Toku; Mizushima, Noboru; Mizuta, Takeshi; Arakawa-Kobayashi, Satoko; Thompson, Craig B; Tsujimoto, Yoshihide
- Abstract
Programmed cell death can be divided into several categories including type I (apoptosis) and type II (autophagic death). The Bcl-2 family of proteins are well-characterized regulators of apoptosis, and the multidomain pro-apoptotic members of this family, such as Bax and Bak, act as a mitochondrial gateway where a variety of apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak double knockout mice are resistant to apoptosis, we found that these cells still underwent a non-apoptotic death after death stimulation. Electron microscopic and biochemical studies revealed that double knockout cell death was associated with autophagosomes/autolysosomes. This non-apoptotic death of double knockout cells was suppressed by inhibitors of autophagy, including 3-methyl adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L). These results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes.
- Publication
Nature cell biology, 2004, Vol 6, Issue 12, p1221
- ISSN
1465-7392
- Publication type
Journal Article
- DOI
10.1038/ncb1192