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Biogenesis and Cargo Selectivity of Autophagosomes
Abstract
Autophagy is a major catabolic pathway in eukaryotes, which is required for the lysosomal/vacuolar degradation of cytoplasmic proteins and organelles. Interest in the autophagy pathway has recently gained momentum largely owing to identification of multiple autophagy-related genes and recognition of its involvement in various physiological conditions. Here we review current knowledge of the molecular mechanisms regulating autophagy in mammals and yeast, specifically the biogenesis of autophagosomes and the selectivity of their cargo recruitment. We discuss the different steps of autophagy, from the signal transduction events that regulate it to the completion of this pathway by fusion with the lysosome/vacuole. We also review research on the origin of the autophagic membrane, the molecular mechanism of autophagosome formation, and the roles of two ubiquitin-like protein families and other structural elements that are essential for this process. Finally, we discuss the various modes of autophagy and highlight their functional relevance for selective degradation of specific cargos.
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“Although autophagic cargo can be trapped passively within the autophagosome in nonselective autophagy, direct substrate recruitment to phagophores in selective autophagy is mediated by a series of receptor proteins (e.g., SQSTM1/p62 [sequestosome 1], NBR1, AMBRA1) that contain both an LC3-interacting region (LIR) and separate motifs for binding polyubiquitinated proteins [41].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [41]
In the citing paper
“Expansion then occurs through maturation of the extending phagophore membrane guided by the ATG12–ATG5-ATG16L1 complex, catalyzing insertion of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) into the phagophore membrane [40,41].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [41]
In the citing paper
“Before membrane insertion, the unbound and immature LC3 precursor protein (LC3-I) undergoes proteolytic processing by ATG4, and conjugation to phosphatidylethanolamine through ATG7 and ATG3. The resulting mature, lipidated isoform (LC3-II) is incorporated into the phagophore membrane [41].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [41]
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Metadata
- Authors
- Weidberg, H., Shvets, E., & Elazar, Z.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Weidberg, Hilla
- Shvets, Elena
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2011-07-07
- Volume
- 80
- Issue
- 1
- Pages
- 125-156
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2052470191
- Cited by
- 466
- References
- 227
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 15 · 2023: 14 · 2022: 24 · 2021: 26 · 2020: 21 · 2019: 28 · 2018: 25 · 2017: 31 · 2016: 40 · 2015: 38 · 2014: 46 · 2013: 59 · 2012: 68
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cell Biology › Cellular transport and secretion
- Keywords
- autophagy, autophagosome formation, selective autophagy, autophagosome-lysosome fusion, ubiquitin-like proteins, autophagy-related genes, signal transduction, yeast autophagy, cytoplasmic degradation
- MeSH terms
- Animals, Autophagy, Intracellular Membranes, Phagosomes, Yeasts, Organelles, Signal Transduction, Biomarkers
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