spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 28 Jun 2005
doi: 10.1242/jcs.02447

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.02447v1
118/14/3091    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by González-Polo, R.-A.
Right arrow Articles by Kroemer, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by González-Polo, R.-A.
Right arrow Articles by Kroemer, G.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death


Rosa-Ana González-Polo, Patricia Boya, Anne-Laure Pauleau, Abdelali Jalil, Nathanael Larochette, Sylvie Souquère, Eeva-Liisa Eskelinen, Gérard Pierron, Paul Saftig, and Guido Kroemer*
* Author for correspondence (e-mail: kroemer{at}igr.fr)

Autophagic cell death is morphologically characterized by an accumulation of autophagic vacuoles. Here, we show that inactivation of LAMP2 by RNA interference or by homologous recombination leads to autophagic vacuolization in nutrient-depleted cells. Cells that lack LAMP2 expression showed an enhanced accumulation of vacuoles carrying the marker LC3, yet a decreased colocalization of LC3 and lysosomes, suggesting that the fusion between autophagic vacuoles and lysosomes was inhibited. While a fraction of mitochondria from starved LAMP2-expressing cells colocalized with lysosomal markers, within autophagolysosomes, no such colocalization was found on removal of LAMP2 from the experimental system. Of note, LAMP1 depletion had no such effects and did not aggravate the phenotype induced by LAMP2-specific small interfering RNA. Serum and amino acid-starved LAMP2-negative cells exhibited an accumulation of autophagic vacuoles and then succumbed to cell death with hallmarks of apoptosis such as loss of the mitochondrial transmembrane potential, caspase activation and chromatin condensation. While caspase inhibition retarded cell death, it had no protective effect on mitochondria. Stabilization of mitochondria by overexpression of Bcl-2 or the mitochondrion-targeted cytomegalovirus protein vMIA, however, blocked all signs of apoptosis. Neither caspase inhibition nor mitochondrial stabilization antagonized autophagic vacuolization in LAMP2-deficient cells. Altogether, these data indicate that accumulation of autophagic vacuoles can precede apoptotic cell death. These findings argue against the clear-cut distinction between type 1 (apoptotic) and type 2 (autophagic) cell death.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
N. Sasi, M. Hwang, J. Jaboin, I. Csiki, and B. Lu
Regulated cell death pathways: New twists in modulation of BCL2 family function
Mol. Cancer Ther., June 1, 2009; 8(6): 1421 - 1429.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol Ind HealthHome page
A Ray, S Roy, S Agarwal, and S Bhattacharya
As2O3 toxicity in rat hepatocytes: manifestation of caspase-mediated apoptosis
Toxicology and Industrial Health, November 1, 2008; 24(10): 643 - 653.
[Abstract] [PDF]

Home page
 JCBHome page
M. Degtyarev, A. De Maziere, C. Orr, J. Lin, B. B. Lee, J. Y. Tien, W. W. Prior, S. van Dijk, H. Wu, D. C. Gray, et al.
Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents
J. Cell Biol., October 6, 2008; 183(1): 101 - 116.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. Wong, J. Zhang, X. Si, G. Gao, I. Mao, B. M. McManus, and H. Luo
Autophagosome Supports Coxsackievirus B3 Replication in Host Cells
J. Virol., September 15, 2008; 82(18): 9143 - 9153.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D.-S. Yang, A. Kumar, P. Stavrides, J. Peterson, C. M. Peterhoff, M. Pawlik, E. Levy, A. M. Cataldo, and R. A. Nixon
Neuronal Apoptosis and Autophagy Cross Talk in Aging PS/APP Mice, a Model of Alzheimer's Disease
Am. J. Pathol., September 1, 2008; 173(3): 665 - 681.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. Nishida, O. Yamaguchi, and K. Otsu
Crosstalk Between Autophagy and Apoptosis in Heart Disease
Circ. Res., August 15, 2008; 103(4): 343 - 351.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Han, W. Hou, L. A. Goldstein, C. Lu, D. B. Stolz, X.-M. Yin, and H. Rabinowich
Involvement of Protective Autophagy in TRAIL Resistance of Apoptosis-defective Tumor Cells
J. Biol. Chem., July 11, 2008; 283(28): 19665 - 19677.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. Singletary and J. Milner
Diet, Autophagy, and Cancer: A Review
Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1596 - 1610.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Apel, I. Herr, H. Schwarz, H. P. Rodemann, and A. Mayer
Blocked Autophagy Sensitizes Resistant Carcinoma Cells to Radiation Therapy
Cancer Res., March 1, 2008; 68(5): 1485 - 1494.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Tiwari, V. K. Bajpai, A. A. Sahasrabuddhe, A. Kumar, R. A. Sinha, S. Behari, and M. M. Godbole
Inhibition of N-(4-hydroxyphenyl)retinamide-induced autophagy at a lower dose enhances cell death in malignant glioma cells
Carcinogenesis, March 1, 2008; 29(3): 600 - 609.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Patschan, J. Chen, A. Polotskaia, N. Mendelev, J. Cheng, D. Patschan, and M. S. Goligorsky
Lipid mediators of autophagy in stress-induced premature senescence of endothelial cells
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1119 - H1129.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
N. F. Trincheri, C. Follo, G. Nicotra, C. Peracchio, R. Castino, and C. Isidoro
Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and on the formation of autophagolysosomes
Carcinogenesis, February 1, 2008; 29(2): 381 - 389.
[Abstract] [Full Text] [PDF]

Home page
 Proc R Soc BHome page
S. R Dunn, C. E Schnitzler, and V. M Weis
Apoptosis and autophagy as mechanisms of dinoflagellate symbiont release during cnidarian bleaching: every which way you lose
Proc R Soc B, December 22, 2007; 274(1629): 3079 - 3085.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. K. Amaravadi and C. B. Thompson
The Roles of Therapy-Induced Autophagy and Necrosis in Cancer Treatment
Clin. Cancer Res., December 15, 2007; 13(24): 7271 - 7279.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Brabec-Zaruba, U. Berka, D. Blaas, and R. Fuchs
Induction of Autophagy Does Not Affect Human Rhinovirus Type 2 Production
J. Virol., October 1, 2007; 81(19): 10815 - 10817.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. J. Marsh, C. Soden, C. Alarcon, B. L. Wicksteed, K. Yaekura, A. J. Costin, G. P. Morgan, and C. J. Rhodes
Regulated Autophagy Controls Hormone Content in Secretory-Deficient Pancreatic Endocrine {beta}-Cells
Mol. Endocrinol., September 1, 2007; 21(9): 2255 - 2269.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. Liao, Y. Yao, J. Liu, Z. Yu, S. Cheung, A. Xie, X. Liang, and X. Bi
Cholesterol Accumulation Is Associated with Lysosomal Dysfunction and Autophagic Stress in Npc1 / Mouse Brain
Am. J. Pathol., September 1, 2007; 171(3): 962 - 975.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
R. A. Gonzalez-Polo, M. Niso-Santano, M. A. Ortiz-Ortiz, A. Gomez-Martin, J. M. Moran, L. Garcia-Rubio, J. Francisco-Morcillo, C. Zaragoza, G. Soler, and J. M. Fuentes
Inhibition of Paraquat-Induced Autophagy Accelerates the Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells
Toxicol. Sci., June 1, 2007; 97(2): 448 - 458.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
F. Demarchi, C. Bertoli, T. Copetti, I. Tanida, C. Brancolini, E.-L. Eskelinen, and C. Schneider
Calpain is required for macroautophagy in mammalian cells
J. Cell Biol., November 20, 2006; 175(4): 595 - 605.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
L. Schaheen, G. Patton, and H. Fares
Suppression of the cup-5 mucolipidosis type IV-related lysosomal dysfunction by the inactivation of an ABC transporter in C. elegans
Development, October 1, 2006; 133(19): 3939 - 3948.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. C. Massey, S. Kaushik, G. Sovak, R. Kiffin, and A. M. Cuervo
Consequences of the selective blockage of chaperone-mediated autophagy
PNAS, April 11, 2006; 103(15): 5805 - 5810.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Fanin, A. C. Nascimbeni, L. Fulizio, M. Spinazzi, P. Melacini, and C. Angelini
Generalized Lysosome-Associated Membrane Protein-2 Defect Explains Multisystem Clinical Involvement and Allows Leukocyte Diagnostic Screening in Danon Disease
Am. J. Pathol., April 1, 2006; 168(4): 1309 - 1320.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. J. Shacka, B. J. Klocke, M. Shibata, Y. Uchiyama, G. Datta, R. E. Schmidt, and K. A. Roth
Bafilomycin A1 Inhibits Chloroquine-Induced Death of Cerebellar Granule Neurons
Mol. Pharmacol., April 1, 2006; 69(4): 1125 - 1136.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005