ATG7(2) 与代谢蛋白相互作用并调节中枢能量代谢

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Traffic Pub Date : 2024-04-11 DOI:10.1111/tra.12933
Kevin Ostacolo, Adrián López García de Lomana, Clémence Larat, Valgerdur Hjaltalin, Kristrun Yr Holm, Sigríður S. Hlynsdóttir, Margaret Soucheray, Linda Sooman, Ottar Rolfsson, Nevan J. Krogan, Eirikur Steingrimsson, Danielle L. Swaney, Margret H. Ogmundsdottir
{"title":"ATG7(2) 与代谢蛋白相互作用并调节中枢能量代谢","authors":"Kevin Ostacolo, Adrián López García de Lomana, Clémence Larat, Valgerdur Hjaltalin, Kristrun Yr Holm, Sigríður S. Hlynsdóttir, Margaret Soucheray, Linda Sooman, Ottar Rolfsson, Nevan J. Krogan, Eirikur Steingrimsson, Danielle L. Swaney, Margret H. Ogmundsdottir","doi":"10.1111/tra.12933","DOIUrl":null,"url":null,"abstract":"Macroautophagy/autophagy is an essential catabolic process that targets a wide variety of cellular components including proteins, organelles, and pathogens. ATG7, a protein involved in the autophagy process, plays a crucial role in maintaining cellular homeostasis and can contribute to the development of diseases such as cancer. ATG7 initiates autophagy by facilitating the lipidation of the ATG8 proteins in the growing autophagosome membrane. The noncanonical isoform ATG7(2) is unable to perform ATG8 lipidation; however, its cellular regulation and function are unknown. Here, we uncovered a distinct regulation and function of <jats:italic>ATG7(2)</jats:italic> in contrast with <jats:italic>ATG7(1)</jats:italic>, the canonical isoform. First, affinity‐purification mass spectrometry analysis revealed that ATG7(2) establishes direct protein–protein interactions (PPIs) with metabolic proteins, whereas ATG7(1) primarily interacts with autophagy machinery proteins. Furthermore, we identified that ATG7(2) mediates a decrease in metabolic activity, highlighting a novel splice‐dependent function of this important autophagy protein. Then, we found a divergent expression pattern of <jats:italic>ATG7(1)</jats:italic> and <jats:italic>ATG7(2)</jats:italic> across human tissues. Conclusively, our work uncovers the divergent patterns of expression, protein interactions, and function of ATG7(2) in contrast to ATG7(1). These findings suggest a molecular switch between main catabolic processes through isoform‐dependent expression of a key autophagy gene.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ATG7(2) Interacts With Metabolic Proteins and Regulates Central Energy Metabolism\",\"authors\":\"Kevin Ostacolo, Adrián López García de Lomana, Clémence Larat, Valgerdur Hjaltalin, Kristrun Yr Holm, Sigríður S. Hlynsdóttir, Margaret Soucheray, Linda Sooman, Ottar Rolfsson, Nevan J. Krogan, Eirikur Steingrimsson, Danielle L. Swaney, Margret H. Ogmundsdottir\",\"doi\":\"10.1111/tra.12933\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Macroautophagy/autophagy is an essential catabolic process that targets a wide variety of cellular components including proteins, organelles, and pathogens. ATG7, a protein involved in the autophagy process, plays a crucial role in maintaining cellular homeostasis and can contribute to the development of diseases such as cancer. ATG7 initiates autophagy by facilitating the lipidation of the ATG8 proteins in the growing autophagosome membrane. The noncanonical isoform ATG7(2) is unable to perform ATG8 lipidation; however, its cellular regulation and function are unknown. Here, we uncovered a distinct regulation and function of <jats:italic>ATG7(2)</jats:italic> in contrast with <jats:italic>ATG7(1)</jats:italic>, the canonical isoform. First, affinity‐purification mass spectrometry analysis revealed that ATG7(2) establishes direct protein–protein interactions (PPIs) with metabolic proteins, whereas ATG7(1) primarily interacts with autophagy machinery proteins. Furthermore, we identified that ATG7(2) mediates a decrease in metabolic activity, highlighting a novel splice‐dependent function of this important autophagy protein. Then, we found a divergent expression pattern of <jats:italic>ATG7(1)</jats:italic> and <jats:italic>ATG7(2)</jats:italic> across human tissues. Conclusively, our work uncovers the divergent patterns of expression, protein interactions, and function of ATG7(2) in contrast to ATG7(1). These findings suggest a molecular switch between main catabolic processes through isoform‐dependent expression of a key autophagy gene.\",\"PeriodicalId\":23207,\"journal\":{\"name\":\"Traffic\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Traffic\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1111/tra.12933\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Traffic","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/tra.12933","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

大自噬/自噬是一种重要的分解代谢过程,它以包括蛋白质、细胞器和病原体在内的多种细胞成分为目标。ATG7是一种参与自噬过程的蛋白质,它在维持细胞稳态方面起着至关重要的作用,并可能导致癌症等疾病的发生。ATG7 通过促进 ATG8 蛋白在不断生长的自噬体膜上脂化来启动自噬。非规范异构体 ATG7(2) 无法进行 ATG8 脂化,但其细胞调控和功能尚不清楚。在这里,我们发现了 ATG7(2) 与 ATG7(1)(典型异构体)不同的调控和功能。首先,亲和纯化质谱分析表明,ATG7(2)与代谢蛋白建立了直接的蛋白-蛋白相互作用(PPIs),而ATG7(1)主要与自噬机制蛋白相互作用。此外,我们还发现 ATG7(2) 能介导代谢活性的降低,这突显了这一重要自噬蛋白的一种新的剪接依赖性功能。然后,我们发现 ATG7(1) 和 ATG7(2) 在人体组织中的表达模式存在差异。最后,我们的研究揭示了 ATG7(2) 与 ATG7(1) 在表达、蛋白相互作用和功能方面的不同模式。这些发现表明,主要分解代谢过程之间的分子转换是通过一个关键自噬基因的同工酶依赖性表达实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
ATG7(2) Interacts With Metabolic Proteins and Regulates Central Energy Metabolism
Macroautophagy/autophagy is an essential catabolic process that targets a wide variety of cellular components including proteins, organelles, and pathogens. ATG7, a protein involved in the autophagy process, plays a crucial role in maintaining cellular homeostasis and can contribute to the development of diseases such as cancer. ATG7 initiates autophagy by facilitating the lipidation of the ATG8 proteins in the growing autophagosome membrane. The noncanonical isoform ATG7(2) is unable to perform ATG8 lipidation; however, its cellular regulation and function are unknown. Here, we uncovered a distinct regulation and function of ATG7(2) in contrast with ATG7(1), the canonical isoform. First, affinity‐purification mass spectrometry analysis revealed that ATG7(2) establishes direct protein–protein interactions (PPIs) with metabolic proteins, whereas ATG7(1) primarily interacts with autophagy machinery proteins. Furthermore, we identified that ATG7(2) mediates a decrease in metabolic activity, highlighting a novel splice‐dependent function of this important autophagy protein. Then, we found a divergent expression pattern of ATG7(1) and ATG7(2) across human tissues. Conclusively, our work uncovers the divergent patterns of expression, protein interactions, and function of ATG7(2) in contrast to ATG7(1). These findings suggest a molecular switch between main catabolic processes through isoform‐dependent expression of a key autophagy gene.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Traffic
Traffic 生物-细胞生物学
CiteScore
8.10
自引率
2.20%
发文量
50
审稿时长
2 months
期刊介绍: Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.
期刊最新文献
Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes. Intercellular Mitochondrial Transfer: The Novel Therapeutic Mechanism for Diseases. Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways. Dissociation of Drosophila Evi-Wg Complex Occurs Post Apical Internalization in the Maturing Acidic Endosomes. Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1