The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Control of autophagy initiation by phosphoinositide 3‐phosphatase jumpy
Open accessAbstract
The majority of studies on autophagy, a cytoplasmic homeostasis pathway of broad biological and medical significance, have been hitherto focused on the phosphatidylinositol 3-kinases as the regulators of autophagy. Here, we addressed the reverse process driven by phosphoinositide phosphatases and uncovered a key negative regulatory role in autophagy of a phosphatidylinositol 3-phosphate (PI3P) phosphatase Jumpy (MTMR14). Jumpy associated with autophagic isolation membranes and early autophagosomes, defined by the key factor Atg16 necessary for proper localization and development of autophagic organelles. Jumpy orchestrated orderly succession of Atg factors by controlling recruitment to autophagic membranes of the sole mammalian Atg factor that interacts with PI3P, WIPI-1 (Atg18), and by affecting the distribution of Atg9 and LC3, the two Atg factors controlling organization and growth of autophagic membranes. A catalytically inactive Jumpy mutant, R336Q, found in congenital disease centronuclear myopathy, lost the ability to negatively regulate autophagy. This work reports for the first time that initiation of autophagy is controlled not only by the forward reaction of generating PI3P through a lipid kinase but that its levels are controlled by a specific PI3P phosphatase, which when defective can lead to human disease.
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“Furthermore, mounting evidence shows that autophagy is regulated by distinct mechanisms in different cell types [11–26], and these cell type-specific mechanisms underlie the differential vulnerability of separate tissues to autophagy mutations, resulting in heterogenous manifestations of disease.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [20]
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“For instance, centronuclear myopathy is caused by mutations in the genes encoding MTM1 (myotubularin1) or MTMR14/Jumpy (myotubularin related protein 14) [17,20].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [20]
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“These loss-of-function mutations prevent these enzymes from metabolizing phosphoinositides required for autophagy, thereby disinhibiting autophagy flux and muscle atrophy [17,20].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [20]
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Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
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How to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · cited 1×
“To discern whether LC3-II increase following Jumpy or MTMR6 knock-downs was due to autophagy stimulation or inhibition of LC3-II degradation, Bafilomycin A1 (BafA1) and lysosomal protease inhibitors were added during the 30-min treatment (Mizushima and Yoshimori, 2007).”
Kimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,237
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
The Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationPhosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
The autophagosome: origins unknown, biogenesis complex
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3696 · Cited by 1,371
Metadata
- Authors
- Vergne, I., Roberts, E., Elmaoued, R. A., Tosch, V., Delgado, M. A., Proikas‐Cezanne, T., Laporte, J., & Deretic, V.
- Affiliations
- University of New Mexico (US)
- Centre National de la Recherche Scientifique (FR)
- University of Tübingen (DE)
- Corresponding author
- Vergne, Isabelle
- Deretic, Vojo
- Venue
- The EMBO Journal
- Published
- 2009-07-09
- Volume
- 28
- Issue
- 15
- Pages
- 2244-2258
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2726690
- OpenAlex
- W2103545941
- Cited by
- 270
- References
- 55
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 12 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 23 · 2015: 22 · 2014: 25 · 2013: 22 · 2012: 29
- FWCI
- 20.69
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-09-10)
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 773)
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- National Institutes of Health
- School of Medicine, University of New Mexico
- National Institute of Allergy and Infectious Diseases (R01AI042999, AI 45148, R01AI045148, R37AI042999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy initiation, Atg16, Atg9, LC3, autophagosome formation, centronuclear myopathy, phosphatidylinositol 3-phosphate
- MeSH terms
- Animals, Autophagy, Cell Line, Humans, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Sequence Analysis, DNA, Amino Acid Substitution, Mutation, Missense, Myopathies, Structural, Congenital, Mice
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