The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death
Abstract
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.
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Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
The role of autophagy during the early neonatal starvation period
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Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
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Self-citationYue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
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Self-citationThe adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal
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“1 control vector (Neo), with human Bcl-2 (Bcl-2) or the cytomegalovirus UL37 exon 1 gene coding for vMIA (viral mitochondrial inhibitor of apoptosis, kindly provided by V. Goldmacher, Immunogen Inc., Cambridge, MA) (Belzacq et al., 2001; Goldmacher et al., 1999; Vieira et al., 2001).”
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
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Self-citationClassification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Metadata
- Authors
- González-Polo, R.-A., Boya, P., Pauleau, A.-L., Jalil, A., Larochette, N., Souquère, S., Eskelinen, E.-L., Pierron, G., Saftig, P., & Kroemer, G.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2005-07-15
- Volume
- 118
- Issue
- 14
- Pages
- 3091-3102
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2003887174
- Cited by
- 524
- References
- 8
- FWCI
- 20.50
- Type
- journal article
- Language
- en
- Open access
- closed
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- González-Polo, R.-A., Boya, P., Pauleau, A.-L., Jalil, A., Larochette, N., Souquère, S., Eskelinen, E.-L., Pierron, G., Saftig, P., & Kroemer, G. (2005). The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. Journal of Cell Science. https://doi.org/10.1242/jcs.02447
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