Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes

Shvets, Elena; Abada, Adi; Weidberg, Hilla; Elazar, Zvulun

doi:10.4161/auto.7.7.15279

Cited by 54 publications

(43 citation statements)

References 15 publications

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“…Our findings indicated that FAS interacts with Atg8 in an N-terminaldependent manner. The N terminal of Atg8 reportedly participates in adaptor recruitment and protein recognition (15,16). FAS degradation was indeed found to be dependent on its interaction with Atg8, further supporting selective degradation.…”

Section: Discussionmentioning

confidence: 72%

“…Atg8 is a key factor in the selective delivery of cargo proteins for degradation. The N-terminal region of Atg8 has been shown to participate in adaptor recruitment and protein recognition (15,16). In searching for potential cargo or machinery proteins that interact with Atg8, we performed immunoprecipitation experiments on Atg8-null cells transformed with GFP-Atg8 or with GFP-Atg8 lacking the first (GFP-Atg8ΔN8) or both (GFP-Atg8ΔN24) N-terminal α-helices.…”

Section: Fas Is Preferentially Degraded By Autophagy Under Nitrogen Smentioning

confidence: 99%

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Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast

Shpilka

Welter

Borovsky

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Autophagy, an evolutionarily conserved intracellular catabolic process, leads to the degradation of cytosolic proteins and organelles in the vacuole/lysosome. Different forms of selective autophagy have recently been described. Starvation-induced protein degradation, however, is considered to be nonselective. Here we describe a novel interaction between autophagy-related protein 8 (Atg8) and fatty acid synthase (FAS), a pivotal enzymatic complex responsible for the entire synthesis of C16-and C18-fatty acids in yeast. We show that although FAS possesses housekeeping functions, under starvation conditions it is delivered to the vacuole for degradation by autophagy in a Vac8-and Atg24-dependent manner. We also provide evidence that FAS degradation is essential for survival under nitrogen deprivation. Our results imply that during nitrogen starvation specific proteins are preferentially recruited into autophagosomesA utophagy is a major cellular catabolic pathway in eukaryotes, responsible for the degradation of organelles and large protein aggregates. This process is induced under various stress conditions, such as amino acid starvation, hypoxia, and oxidative stress (1, 2).In yeast (Saccharomyces cerevisiae), nitrogen starvation is known to induce macroautophagy (hereafter termed autophagy), which is essential mainly for supplementing amino acids needed for protein synthesis (3). Autophagy has long been considered to be a nonselective process except for the recruitment of ribosomes into autophagosomes, which was suggested to be selective under conditions of nitrogen starvation (4). Selective autophagy is thought to play a role mainly in cell homeostasis, and it uses the core autophagy genes and varying sets of proteins for different cargos (5). Autophagy-related protein 8 (Atg8), a key autophagic factor essential for autophagosome biogenesis, also plays a major role in selective autophagy by recruiting cargo proteins into the autophagosome (6).Fatty acid synthase (FAS) is a large (2.6 MDa), essential enzymatic complex responsible for the entire synthesis of C16-and C18-fatty acids (7). FAS is composed of two subunits, Fas1 (Fasβ) and Fas2 (Fasα), which are arranged in an α 6 β 6 macromolecular complex. Deletion of one of the FAS subunits has been shown to result in degradation of the other (8). Whereas the unassembled Fas2 subunit is short-lived and degrades in the proteasome, the unassembled Fas1, once induced, is degraded by autophagy. Moreover, the FAS complex is known to be delivered to the vacuole under potassium acetate starvation (8).Here we investigated the role of autophagy in the degradation of the FAS complex. We report a physical interaction between Atg8 and FAS, and show that autophagy preferentially degrades FAS and decreases its activity during nitrogen starvation. We suggest that the selective degradation of FAS under nitrogen starvation requires the participation of Atg24 and Vac8, two factors that each play a role in selective autophagy (9-12). Finally, we show that FAS degradation is important ...

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Section: Discussionmentioning

confidence: 72%

Section: Fas Is Preferentially Degraded By Autophagy Under Nitrogen Smentioning

confidence: 99%

Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast

Shpilka

Welter

Borovsky

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The autophagy receptor p62/SQSTM1 binds very well to all ATG8 family proteins in in vitro binding studies. However, for selective autophagy of p62/SQSTM1, it has been found that LC3B is required and not the GABARAP subfamily (43,44).…”

Section: Discussionmentioning

confidence: 99%

FYCO1 Contains a C-terminally Extended, LC3A/B-preferring LC3-interacting Region (LIR) Motif Required for Efficient Maturation of Autophagosomes during Basal Autophagy

Olsvik

Lamark

Takagi

et al. 2015

Journal of Biological Chemistry

112

135

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Background: FYCO1 binds to LC3 and is involved in transport of autophagosomes. Results: FYCO1 uses a C-terminally extended LIR motif for specific interaction with LC3A/B stimulating autophagosome maturation during basal autophagy. Conclusion:The transport adaptor FYCO1 engages in a specific interaction with LC3A/B to stimulate autophagosome maturation. Significance: This work will lead to an increased understanding of LIR interactions and the role of FYCO1 in autophagy.

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“…p62 binds to both soluble LC3 and GATE-16, but it interacts only with lipidated LC3, not lipidated GATE-16 (23). Thus, the recruitment of p62 into autophagosomes specifically depends on LC3.…”

mentioning

confidence: 99%

Gene Deletion of Gabarap Enhances Nlrp3 Inflammasome-Dependent Inflammatory Responses

Zhang

et al. 2013

The Journal of Immunology

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The γ-aminobutyric acid A receptor–associated protein (Gabarap) functions in γ-aminobutyric acid A receptor trafficking and postsynaptic localization in neurons, but its physiological roles in other systems have not been studied. In this study, we report that Gabarap-deficient mice are more susceptible to mortality in two sepsis models. An underlying mechanism of this higher mortality rate in Gabarap−/− septic mice is the higher level of proinflammatory cytokine expression in Gabarap−/− mice versus wild-type mice. In vitro studies show that Nlrp3 inflammasome activation is enhanced by Gabarap deficiency, as evidenced by more casapse-1 activation, more IL-1β, and more IL-18 secretion in LPS- and ATP-treated Gabarap−/− macrophages. The Gabarap deficiency led to inefficient clearance of damaged mitochondria in LPS plus ATP–treated macrophages, resulting in more mitochondrial ROS and the release of mitochondrial DNA into cytosol. Both ROS and mitochondrial DNA are known to promote inflammasome activation. These results demonstrate that Gabarap functions in the immune system. It is involved in mitochondrial quality control in macrophages, and thus it influences Nlrp3 inflammasome-dependent inflammatory responses.

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Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes

Cited by 54 publications

References 15 publications

Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast

Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast

FYCO1 Contains a C-terminally Extended, LC3A/B-preferring LC3-interacting Region (LIR) Motif Required for Efficient Maturation of Autophagosomes during Basal Autophagy

Gene Deletion of Gabarap Enhances Nlrp3 Inflammasome-Dependent Inflammatory Responses

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