Atg11 is required for initiation of glucose starvation-induced autophagy

Yao, Weijing; Li, Yixing; Wu, Liming; Wu, Choufei; Zhang, Yi; Liu, Jing; He, Zelai; Wu, Xiaoyong; Lu, Chenjun; Wang, Liefeng; Zhong, Huiming; Hong, Zhi; Xu, Shili; Liu, Wei; Yi, Cong

doi:10.1080/15548627.2020.1719724

Cited by 30 publications

(30 citation statements)

References 37 publications

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“…In response to nutrient deficiency, the energy sensor AMPK is activated, which in turn inhibits mTOR complex 1 (mTORC1), leading to activation of the ULK1 kinase, which is important for induction of autophagy (AMPK-mTORC1-ULK1 triad) 91 . Recent findings in yeast have demonstrated that Atg11 is necessary to facilitate interaction between the AMPK homolog Snf1 and the ULK1 homolog Atg1 upon glucose starvation to promote autophagy 93 . The LC3-interacting region (LIR) motif, also known in yeast as the Atg8-family-interacting motif (AIM), in starch-binding domain-containing protein 1 (STBD1) may allow cells to physically link glycogen to GABARAPL1, facilitating the transport of glycogen to lysosomes for degradation (Fig.…”

Section: Autophagy Regulation Of Macromolecule Availabilitymentioning

confidence: 99%

Autophagy in healthy aging and disease

et al. 2021

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Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health.

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Section: Autophagy Regulation Of Macromolecule Availabilitymentioning

confidence: 99%

Autophagy in healthy aging and disease

et al. 2021

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“…After we had completed our directed Y2H screen of the CC2 region, but while verification of mutational effects was still underway, a study was published from another group that used random mutagenesis of the CC2 region combined with Y2H screening to identify a mutation that caused a loss of interaction with Atg9 ( Yao et al, 2020 ). The mutation identified, I569E, is strikingly similar to the I562E and Y565E mutations that were identified here.…”

Section: Resultsmentioning

confidence: 99%

“…The I569E mutation was recently identified by the Yi lab, who discovered that it interfered with Atg11’s interaction with Atg9 and blocked both the cvt pathway and glucose starvation-induced autophagy ( Yao et al, 2020 ). Our data confirms the importance of I569 for Atg11’s interaction with Atg9 but shows that it is also important for Atg11’s interaction with Atg1.…”

Section: Discussionmentioning

confidence: 99%

“…Atg1 is a protein kinase which, along with its obligate partner Atg13, plays both a structural and a regulatory role in autophagosome formation ( Abeliovich et al, 2000 ; Kamada et al, 2000 ; Cheong et al, 2008 ). Atg11 activates Atg1 by clustering it together on the surface of the cargo ( Kamber et al, 2015 ; Torggler et al, 2016 ) and also directly recruits Atg9 to the site of autophagosome formation ( He et al, 2006 ; Yao et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Mapping Critical Residues in ATG11’s Coiled-Coil 2 Domain that Block Multiple Interactions and Disrupt Selective Autophagy

Meyer

Winzeler

Taylor

et al. 2022

Front. Cell Dev. Biol.

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Selective autophagy is a conserved subcellular process that maintains the health of eukaryotic cells by targeting damaged or toxic cytoplasmic components to the vacuole/lysosome for degradation. A key player in the initiation of selective autophagy in S. Cerevisiae (baker’s yeast) is a large adapter protein called Atg11. Atg11 has multiple predicted coiled-coil domains and intrinsically disordered regions, is known to dimerize, and binds and organizes other essential components of the autophagosome formation machinery, including Atg1 and Atg9. We performed systematic directed mutagenesis on the coiled-coil 2 domain of Atg11 in order to map which residues were required for its structure and function. Using yeast-2-hybrid and coimmunoprecipitation, we found only three residues to be critical: I562, Y565, and I569. Mutation of any of these, but especially Y565, could interfere with Atg11 dimerization and block its interaction with Atg1 and Atg9, thereby inactivating selective autophagy.

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“…Msn2 and Gis1 can activate the transcription of the genes encoding heat shock proteins (e.g., Hsp12 , Hsp26 , Ssa3 ) upon nutrient limitation [ 137 ]. The PKA, SNF1, TOR and PHO pathways can regulate the expression of genes involved in autophagy (e.g., Atg8 , Atg11 , Atg13 ) and trehalose metabolism (e.g., Tps1 , Tps2 , Nth1 ), while the PKA and TOR pathways control the expression of genes involved in amino acid biosynthesis (e.g., Gcn2 , Gcn4 ) and ribosome biogenesis (e.g., Fhl1 , Maf1 , Rps ) [ 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ].…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Analysis of Nutrient Signaling Pathways Conserved in Arbuscular Mycorrhizal Fungi

Xiao-qin

Tang

et al. 2021

Microorganisms

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Arbuscular mycorrhizal (AM) fungi form a mutualistic symbiosis with a majority of terrestrial vascular plants. To achieve an efficient nutrient trade with their hosts, AM fungi sense external and internal nutrients, and integrate different hierarchic regulations to optimize nutrient acquisition and homeostasis during mycorrhization. However, the underlying molecular networks in AM fungi orchestrating the nutrient sensing and signaling remain elusive. Based on homology search, we here found that at least 72 gene components involved in four nutrient sensing and signaling pathways, including cAMP-dependent protein kinase A (cAMP-PKA), sucrose non-fermenting 1 (SNF1) protein kinase, target of rapamycin kinase (TOR) and phosphate (PHO) signaling cascades, are well conserved in AM fungi. Based on the knowledge known in model yeast and filamentous fungi, we outlined the possible gene networks functioning in AM fungi. These pathways may regulate the expression of downstream genes involved in nutrient transport, lipid metabolism, trehalase activity, stress resistance and autophagy. The RNA-seq analysis and qRT-PCR results of some core genes further indicate that these pathways may play important roles in spore germination, appressorium formation, arbuscule longevity and sporulation of AM fungi. We hope to inspire further studies on the roles of these candidate genes involved in these nutrient sensing and signaling pathways in AM fungi and AM symbiosis.

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Atg11 is required for initiation of glucose starvation-induced autophagy

Cited by 30 publications

References 37 publications

Autophagy in healthy aging and disease

Autophagy in healthy aging and disease

Mapping Critical Residues in ATG11’s Coiled-Coil 2 Domain that Block Multiple Interactions and Disrupt Selective Autophagy

Genome-Wide Analysis of Nutrient Signaling Pathways Conserved in Arbuscular Mycorrhizal Fungi

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