Cited by 2,083Autophagy in Disease and TherapyCellular transport and secretionUbiquitin and proteasome pathways

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The machinery of macroautophagy

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Feng, Yuchen, He, Ding, Yao, Zhiyuan, Klionsky, Daniel J·2014·Cell Research

DOI 10.1038/cr.2013.168PMC PMC3879710

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Abstract

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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Authors: Feng, Y., He, D., Yao, Z., & Klionsky, D. J.
Affiliations: University of Michigan (US)
Corresponding author: Klionsky, Daniel J
ORCID: Feng, Yuchen
Yao, Zhiyuan
Klionsky, Daniel J
Venue: Cell Research
Publisher: Springer Science and Business Media LLC
Published: 2013-12-24
Volume: 24
Issue: 1
Pages: 24-41
ISSN: 1001-0602 (ISSN-L)
1748-7838
DOI: 10.1038/cr.2013.168
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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