The molecular mechanism of Atg13 function in autophagy induction: What is hidden behind the data?

Popelka, Hana; Klionsky, Daniel J.

doi:10.1080/15548627.2016.1277312

Cited by 18 publications

(15 citation statements)

References 20 publications

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“…To further examine the immunoprecipitation data of ATG101 and its mutants, various constructs were generated for the monitoring of autophagosome formation using GFP-tagged LC3, a well-known autophagy marker [6,33,40,41]. Autophagy was induced by nutrient-starvation, and punctate GFP-LC3 fluorescent signals indicating the recruitment of LC3 protein to autophagosomes were detected in the cytosol (Figure 5(b)).…”

Section: Effect Of the C-terminal Region Of Atg101 On Autophagymentioning

confidence: 99%

“…Besides the differences between the components of the mammalian ULK1 and budding yeast Atg1 complex, ATG13 (Atg13 in budding yeast) in particular is quite dissimilar in size as well as in binding partners [15,32,33]. The HORMA domain in Atg13 from S. cerevisiae (ScAtg13 HORMA ) forms a monomer with a unique β-sheet cap domain [31], whereas mammalian ATG13 HORMA forms a heterodimer with ATG101 [34,35].…”

Section: Introductionmentioning

confidence: 99%

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The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

et al. 2018

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The initiation of macroautophagy/autophagy is tightly regulated by the upstream ULK1 kinase complex, which affects many downstream factors including the PtdIns3K complex. The phosphorylation of the right position at the right time on downstream molecules is governed by proper complex formation. One component of the ULK1 complex, ATG101, known as an accessory protein, is a stabilizer of ATG13 in cells. The WF finger region of ATG101 plays an important role in the recruitment of WIPI1 (WD repeat domain, phosphoinositide interacting protein 1) and ZFYVE1 (zinc finger FYVE-type containing 1). Here, we report that the C-terminal region identified in the structure of the human ATG101-ATG13 complex is responsible for the binding of the PtdIns3K complex. This region adopts a β-strand conformation in free ATG101, but either an α-helix or random coil in our ATG101-ATG13 complex, which protrudes from the core and interacts with other molecules. The C-terminal deletion of ATG101 shows a significant defect in the interaction with PtdIns3K components and subsequently impairs autophagosome formation. This result clearly presents an additional role of ATG101 for bridging the ULK1 and PtdIns3K complexes in the mammalian autophagy process. Abbreviations: ATG: autophagy related; BECN1: beclin 1; GFP: green fluorescent protein; HORMA: Hop1p/Rev7p/MAD2; HsATG13: HORMA domain of ATG13 from Homo sapiens; KO: knockout; MAD2: mitotic arrest deficient 2 like 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PtdIns3K: phosphatidylinositol 3-kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SAXS: small-angle X-ray scattering; ScAtg13: HORMA domain of Atg13 from Sccharomyces cerevisiae; SEC-SAXS: size-exclusion chromatography with small-angle X-ray scattering; SpAtg13: HORMA domain of Atg13 from Schizosaccharomyces pombe; SQSTM1/p62: sequestosome 1; ULK1: unc51-like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; WIPI1: WD repeat domain: phosphoinositide interacting 1; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1.

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Section: Effect Of the C-terminal Region Of Atg101 On Autophagymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

et al. 2018

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“…The top 10 best candidates are as follows: atg13Δ, yjl147cΔ, ylr261cΔ, tif2Δ, meh1Δ, rps29bΔ, dyn1Δ, lst4Δ, atg12Δ, and vps30Δ (atg6Δ). Atg13 functions in vesicle formation, and is required for autophagy 75 . Importantly, Atg13 also functions in the recruitment of Atg14 to the PAS 45 .…”

Section: Nsd Screen Accuracymentioning

confidence: 99%

“…In short, Atg12 mediates the lipidation of Atg8 which in turn will complete the production of an APS from the PAS 80 . The ATG13 gene has been shown to activate the Atg1 protein under nutrient depletion, activating the autophagy pathway 75 . It is also required for vesicle formation and the recruitment of Atg14 to the PAS 75 .…”

Section: Autophagy Related Genesmentioning

confidence: 99%

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A Genomic Screen of Saccharomyces cerevisiae Reveals a Potential Link Between Nonstop Decay and Autophagy

Kazmirchuk¹

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Little has been described about the mechanisms of the Nonstop Decay (NSD) pathway. To discover new genes involved in NSD, we performed a genome wide investigation in Saccharomyces cerevisiae which yielded 446 gene candidates that when deleted, allowed production of a nonstop mRNA. Of the gene families found in our screen, we decided to follow up on the autophagy candidates. First, we used the autophagy inhibiting drug verteporfin to confirm that autophagy does not occur in our candidates. The results confirm our prediction that autophagy is inhibited in our two autophagy candidates. Next, we assessed the abundance of nonstop mRNA using qRT-PCR analysis. This resulted in lower than expected nonstop mRNA abundance relative to the WT, which led us to investigate nonstop protein abundance.Interestingly, we see an increase in the abundance of nonstop protein abundance relative to the WT. Together, our results suggest that NSD may occur through autophagy.ii

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Autophagy in Stem Cell Maintenance and Differentiation

Sahu

Bandyopadhyay²,

Chowdhury³

et al. 2022

Autophagy in Stem Cell Maintenance and Differentiation

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The molecular mechanism of Atg13 function in autophagy induction: What is hidden behind the data?

Cited by 18 publications

References 20 publications

The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

A Genomic Screen of Saccharomyces cerevisiae Reveals a Potential Link Between Nonstop Decay and Autophagy

Autophagy in Stem Cell Maintenance and Differentiation

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