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Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2003
- Publisher :
- The Rockefeller University Press, 2003.
-
Abstract
- Bax and Bak play a redundant but essential role in apoptosis initiated by the mitochondrial release of apoptogenic factors. In addition to their presence at the mitochondrial outer membrane, Bax and Bak can also localize to the ER. Agents that initiate ER stress responses can induce conformational changes and oligomerization of Bax on the ER as well as on mitochondria. In wild-type cells, this is associated with caspase 12 cleavage that is abolished in bax−/−bak−/− cells. In bax−/−bak−/− cells, introduction of Bak mutants selectively targeted to either mitochondria or the ER can induce apoptosis. However, ER-targeted, but not mitochondria-targeted, Bak leads to progressive depletion of ER Ca2+ and induces caspase 12 cleavage. In contrast, mitochondria-targeted Bak leads to enhanced caspase 7 and PARP cleavage in comparison with the ER-targeted Bak. These findings demonstrate that in addition to their functions at mitochondria, Bax and Bak also localize to the ER and function to initiate a parallel pathway of caspase activation and apoptosis.
- Subjects :
- Protein Conformation
Poly ADP ribose polymerase
Bak
Bax
Ca2+
caspase 12
ER
Apoptosis
Endoplasmic Reticulum
Caspase 7
Article
03 medical and health sciences
Mice
0302 clinical medicine
Bcl-2-associated X protein
Stress, Physiological
Proto-Oncogene Proteins
Animals
Calcium Signaling
Caspase
Caspase 12
030304 developmental biology
Cell Line, Transformed
bcl-2-Associated X Protein
0303 health sciences
biology
Endoplasmic reticulum
Membrane Proteins
Cell Biology
Molecular biology
Cell biology
Mitochondria
Protein Transport
Eukaryotic Cells
bcl-2 Homologous Antagonist-Killer Protein
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
Caspases
Mutation
biology.protein
Unfolded protein response
Calcium
biological phenomena, cell phenomena, and immunity
Poly(ADP-ribose) Polymerases
Bcl-2 Homologous Antagonist-Killer Protein
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 162
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....d1cddcbc42097acc60d86ab93047d0a0