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Autophagy fights disease through cellular self-digestion
Open accessAbstract
Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.
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“Proteostasis involves mechanisms for the stabilization of correctly folded proteins, most prominently the heat-shock family of proteins, and mechanisms for the degradation of proteins by the proteasome or the lysosome (Hartl et al., 2011; Koga et al., 2011; Mizushima et al., 2008).”
From The Hallmarks of Aging (2013) · cites this paper as Mizushima et al., 2008
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“The neuroprotective function of macroautophagy has become an interesting focus in neurodegenerative disease, exemplified in Huntington's disease (Menzies et al., 2006;Mizushima et al., 2008), as well as in animal models (Hara et al., 2006;Komatsu et al., 2006).”
From Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies (2008) · cites this paper as Mizushima et al., 2008
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“Three different forms of autophagy have been described in mammalian cells: macroautophagy, microautophagy and chaperone-mediated autophagy (Fig. 3) (Cuervo, 2009; He and Klionsky, 2009; Mizushima et al., 2008).”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Mizushima et al., 2008
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“macro-autophagy (hereafter referred to as autophagy)—a tightly regulated major lysosomal degradation pathway (27–30)—has been implicated in establishing the SASP through the target of rapamycin (TOR) autophagy spatial coupling compartment (TASCC).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [27]
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1 retracted
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Self-citationAPF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p
Wang, K., Liu, C.-Y., Zhou, L.-Y., Wang, J.-X., Wang, M., Zhao, B., Zhao, W.-K., Xu, S.-J., Fan, L.-H., Zhang, X.-J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7779 · Cited by 473
Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival
Efeyan, A., Zoncu, R., Chang, S. H., Gumper, I., Snitkin, H., Wolfson, R. L., Kirak, O., Sabatini, D. M., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11745 · Cited by 473
Luciani, A., Villella, V. R., Esposito, S., Brunetti-Pierri, N., Medina, D., Settembre, C., Gavina, M., Pulze, L., Giardino, I., Pettoello-Mantovani, M., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2090 · Cited by 467
Autophagy activation by rapamycin reduces severity of experimental osteoarthritis
Caramés, B., Hasegawa, A., Taniguchi, N., Miyaki, S., Blanco, F. J., & Lotz, M. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2011-200557 · Cited by 466
Virgin, H. W., & Levine, B. (2009) · Nature Immunology · doi:10.1038/ni.1726 · Cited by 462
Self-citationAutophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
Castillo, E. F., Dekonenko, A., Arko‐Mensah, J., Mandell, M. A., Dupont, N., Jiang, S., Delgado-Vargas, M., Timmins, G. S., Bhattacharya, D., Yang, H., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210500109 · Cited by 462
Autophagy Protects the Proximal Tubule from Degeneration and Acute Ischemic Injury
Kimura, T., Takabatake, Y., Takahashi, A., Kaimori, J.-Y., Matsui, I., Namba, T., Kitamura, H., Niimura, F., Matsusaka, T., Soga, T., et al. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010070705 · Cited by 461
The yeast lysosome-like vacuole: Endpoint and crossroads
Li, S. C., & Kane, P. M. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.08.003 · Cited by 461
Chan, E. Y. W., Longatti, A., McKnight, N. C., & Tooze, S. A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01082-08 · Cited by 411
Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L
Matsunaga, K., Morita, E., Saitoh, T., Akira, S., Ktistakis, N. T., Izumi, T., Noda, T., & Yoshimori, T. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911141 · Cited by 456
Exosomes and Autophagy: Coordinated Mechanisms for the Maintenance of Cellular Fitness
Baixauli, F., López-Otı́n, C., & Mittelbrunn, M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00403 · Cited by 456
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453
Ubiquitin–proteasome pathway and cellular responses to oxidative stress
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Metadata
- Authors
- Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J.
- Affiliations
- Tokyo Medical and Dental University (JP)
- The University of Texas at Dallas (US)
- University of Michigan (US)
- Corresponding author
- Klionsky, Daniel J.
- Venue
- Nature
- Published
- 2008-02
- Volume
- 451
- Issue
- 7182
- Pages
- 1069-1075
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2670399
- OpenAlex
- W1994823455
- Cited by
- 6,452
- References
- 60
- Citations by year
- 2026: 126 · 2025: 233 · 2024: 302 · 2023: 305 · 2022: 361 · 2021: 381 · 2020: 412 · 2019: 392 · 2018: 388 · 2017: 434 · 2016: 439 · 2015: 430 · 2014: 456 · 2013: 400 · 2012: 378
- FWCI
- 35.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- American Cancer Society
- Ellison Medical Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Toray Science Foundation
- National Institutes of Health
- National Institute on Aging (R03AG019834, R01AG021904, R21AG025355)
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy, protein degradation, organelle degradation, cytoprotection, cell death, cancer, neurodegeneration, microbial infection, aging
- MeSH terms
- Aging, Animals, Autophagy, Cell Survival, Humans, Immunity, Innate, Neoplasms, Cell Death, Neurodegenerative Diseases
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