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":"48 1","pages":""},"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\":\"48 1\",\"pages\":\"\"},\"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}
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.
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.