Abstract
BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1-interacting protein, positively regulates the BECLIN 1-dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum-resident BCL-2 (mito-BCL-2 and ER-BCL-2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito-BCL-2; after autophagy induction, AMBRA1 is released from BCL-2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito-BCL-2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1195-1208 |
| Number of pages | 14 |
| Journal | EMBO Journal |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 6 2011 |
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Keywords
- apoptosis
- autophagy
- endoplasmic reticulum
- mitochondria
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Neuroscience(all)
Cite this
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. / Strappazzon, Flavie; Vietri-Rudan, Matteo; Campello, Silvia; Nazio, Francesca; Florenzano, Fulvio; Fimia, Gian Maria; Piacentini, Mauro; Levine, Beth; Cecconi, Francesco.
In: EMBO Journal, Vol. 30, No. 7, 06.04.2011, p. 1195-1208.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy
AU - Strappazzon, Flavie
AU - Vietri-Rudan, Matteo
AU - Campello, Silvia
AU - Nazio, Francesca
AU - Florenzano, Fulvio
AU - Fimia, Gian Maria
AU - Piacentini, Mauro
AU - Levine, Beth
AU - Cecconi, Francesco
PY - 2011/4/6
Y1 - 2011/4/6
N2 - BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1-interacting protein, positively regulates the BECLIN 1-dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum-resident BCL-2 (mito-BCL-2 and ER-BCL-2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito-BCL-2; after autophagy induction, AMBRA1 is released from BCL-2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito-BCL-2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis.
AB - BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1-interacting protein, positively regulates the BECLIN 1-dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum-resident BCL-2 (mito-BCL-2 and ER-BCL-2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito-BCL-2; after autophagy induction, AMBRA1 is released from BCL-2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito-BCL-2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis.
KW - apoptosis
KW - autophagy
KW - endoplasmic reticulum
KW - mitochondria
UR - http://www.scopus.com/inward/record.url?scp=79953796695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953796695&partnerID=8YFLogxK
U2 - 10.1038/emboj.2011.49
DO - 10.1038/emboj.2011.49
M3 - Article
VL - 30
SP - 1195
EP - 1208
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 7
ER -