Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors.

By T. Johansen, T. Lamark. Journal of Molecular Biology, 2020

625 citations recorded by the source corpus.

Selective autophagy relies on soluble or membrane-bound cargo receptors that recognize cargo and bring about autophagosome formation at the cargo. The cargo-bound receptors interact with lipidated ATG8 family proteins anchored in the membrane at the concave side of the forming autophagosome. The interaction is mediated by 15-20 amino acid long sequence motifs called LC3-interacting region (LIR) motifs that bind to the LIR docking site (LDS) of ATG8 proteins. In this review we focus on LIR-ATG8 interactions and the soluble mammalian selective autophagy receptors (SARs). We discuss the roles of ATG8 family proteins as membrane scaffolds in autophagy and the LIR-LDS interaction and how specificity for binding to GABARAP or LC3 subfamily proteins is achieved. We also discuss atypical LIR-LDS interactions and a novel LIR-independent interaction. Recently, it has become clear that several of the soluble cargo receptors are able to recruit components of the core autophagy apparatus to aid in assembling autophagosome formation at the site of cargo sequestration. A model on phagophore recruitment and expansion on a SAR-coated cargo incorporating the latest findings is presented.

Subfields: Cell Biology, Epidemiology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/1bafd8eeafd0344274005e494e6fb415c23a2d55

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In Cell Biology

1. Guido Kroemer
2. D. Klionsky
3. R. Kang
4. S. Martens
5. D. Tang
6. N. Mizushima
7. Beth Levine
8. G. Hotamışlıgil

In Epidemiology

1. Guido Kroemer
2. D. Tang
3. R. Kang
4. D. Klionsky
5. Jiao Liu
6. S. Martens
7. Beth Levine
8. N. Mizushima

In Public Health, Environmental and Occupational Health

1. Guido Kroemer
2. D. Klionsky

Citations in the corpus

• The mitophagy pathway and its implications in human diseases (2023, background): “38 Autophagy adapters are de fi ned as proteins possessing both a ubiquitin-binding domain (UBD) that recognizes ubiquitin-tagged mitochondria and an LC3 interacting region (LIR) that interacts with ATG8 family proteins, which mainly includes sequestosome 1 (P62/SQSTM1), 39 neighbor of BRCA1 gene 1…”
• Autophagy-Dependent Ferroptosis: Machinery and Regulation (2020, background): “In general, the autophagy receptors interact with lipidated LC3 or GABARAP subfamily proteins by LC3-interacting region (LIR) motifs that bind to the LIR docking site (LDS) of Atg8 family proteins in a cargo-dependent manner (Johansen and Lamark, 2020).”
• A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress (2020, background): “Recent studies have shown that autophagy is highly selective (Johansen and Lamark, 2019; Stolz et al., 2014), and is mediated by receptors that recruit specific cargo, such as damaged organelles or protein aggregates.”