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The machinery of macroautophagy
Open accessAbstract
Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.
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“ATG7 is strictly required for autophagosome formation; it is an E1-like activating enzyme present in ubiquitin-like conjugation systems that promotes both cleavage and lipidation of LC3 and GABARAP [43].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [43]
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“ULK1 is considered as the master regulator of autophagy induction, triggering a cascade of signals, through direct phosphorylation of ATG proteins, that culminate in autophagosome formation [3, 43].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [43]
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“Indeed, autophagy functions as a quality control mechanism, maintaining cellular homeostasis by destroying aggregate-prone proteins and damaged organelles [45].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [45]
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Metadata
- Authors
- Feng, Y., He, D., Yao, Z., & Klionsky, D. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Klionsky, Daniel J
- Venue
- Cell Research
- Published
- 2013-12-24
- Volume
- 24
- Issue
- 1
- Pages
- 24-41
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC3879710
- OpenAlex
- W2044621729
- Cited by
- 2,083
- References
- 180
- Citations by year
- 2026: 84 · 2025: 130 · 2024: 193 · 2023: 180 · 2022: 238 · 2021: 215 · 2020: 200 · 2019: 185 · 2018: 177 · 2017: 161 · 2016: 161 · 2015: 109 · 2014: 45 · 2013: 3
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM053396)
- 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 › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- macroautophagy, autophagy machinery, phagophore formation, autophagosomes, autophagy-related proteins, autophagy regulation, lysosomes, cellular homeostasis, cytoprotection, neurodegenerative diseases, cancer, yeast autophagy
- MeSH terms
- Animals, Autophagy, Homeostasis, Humans, Lysosomes, Phagosomes, Pichia, Saccharomyces cerevisiae, Vacuoles, Protein Serine-Threonine Kinases
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