Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Oct. 26, 2024
The acetylation of autophagy protein 9 A (ATG9A) in the lumen endoplasmic reticulum (ER) by ATase1 and ATase2 regulates induction reticulophagy. Analysis ER-specific ATG9A interactome identified calreticulin (CALR), an ER luminal Ca
Language: Английский
Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(15), P. 168489 - 168489
Published: Feb. 10, 2024
Autophagy mediates the degradation and recycling of cellular material in lysosomal system. Dysfunctional autophagy is associated with a plethora diseases including uncontrolled infections, cancer neurodegeneration. In macroautophagy (hereafter autophagy) this encapsulated double membrane vesicles, autophagosomes, which form upon induction autophagy. The precursors to referred as phagophores, first appear small flattened cisternae, gradually enclose cargo they grow. assembly phagophores during initiation has been major subject investigation over past decades. A special focus ATG9, only conserved transmembrane protein among core machinery. majority ATG9 localizes Golgi-derived vesicles. Here we review recent advances breakthroughs regarding our understanding how vesicles it resides serve assemble machinery establish contact sites for autophagosome biogenesis. We also highlight open questions field that need be addressed years come.
Language: Английский
Citations
24
The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(2)
Published: Jan. 2, 2025
Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite its subsequent fusion with endolysosomal organelles and degradation sequestered cargo. ATG9A, key integral protein pathway, best known role in formation expansion phagophores. Here, we report hitherto unappreciated function mammalian ATG9A directing closure. partners IQGAP1 ESCRT-III component CHMP2A to facilitate this final stage formation. Thus, central hub governing all major aspects biogenesis, from unique ATG factor progressive functionalities affecting physiological outputs autophagy.
Language: Английский
Citations
2
Autophagy, Journal Year: 2024, Volume and Issue: 20(11), P. 2373 - 2387
Published: Aug. 4, 2024
Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in year 2000 yeast. Two homologs of ATG9A and ATG9B, have been found mammals. While ATG9B shows a tissue-specific expression pattern, such as placenta pituitary gland, is ubiquitously expressed. Additionally, deficiency leads to severe defects not at molecular cellular levels but also organismal level, suggesting key fundamental roles for ATG9A. The subcellular localization on small vesicles its functional relevance autophagy suggested potential role lipid supply during autophagosome biogenesis. Nevertheless, precise autophagic process has remained long-standing mystery, especially neurons. Recent findings, however, including structural, proteomic, biochemical analyses, provided new insights into function expansion phagophore membrane. In this review, we aim understand various aspects ATG9 (in invertebrates plants)/ATG9A mammals), localization, trafficking, other functions, nonneuronal cells neurons by comparing recent discoveries related ATG9/ATG9A proposing directions future research.
Language: Английский
Citations
4
Autophagy, Journal Year: 2025, Volume and Issue: unknown
Published: April 21, 2025
Rickettsiae are tick-borne pathogens that infect human hosts through poorly characterized mechanisms. Herein, we report ATG9 (autophagy related 9) plays a previously unrecognized role in inhibiting Rickettsia binding to the host cell surface. Unexpectedly, this new function of is likely independent macroautophagy/autophagy. Instead, acts as defending factor by XRCC6/KU70, receptor outer-membrane protein rOmpB. Both and rOmpB bind DNA-binding domain XRCC6, suggesting competitive for occupying site abrogate binding. Furthermore, show rapamycin transcriptionally activates inhibits rOmpB-mediated infection mouse model. Collectively, our study reveals novel innate mechanism regulating suggests agonists May be useful developing therapeutic strategies intervention rickettsial diseases.
Language: Английский
Citations
0
Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(15), P. 168691 - 168691
Published: June 27, 2024
Language: Английский
Citations
3
Molecular Biology of the Cell, Journal Year: 2024, Volume and Issue: 35(10)
Published: Aug. 7, 2024
Subversion of cellular membranes and membrane proliferation are used by positive-strand RNA viruses to build viral replication organelles (VROs) that support virus replication. The biogenesis the membranous VROs requires major changes in lipid metabolism transfer infected cells. In this work, we show tomato bushy stunt (TBSV) hijacks Atg2 autophagy related protein with bulk activity into via interaction TBSV p33 protein. Deletion yeast knockdown
Language: Английский
Citations
3
The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(7)
Published: April 4, 2024
Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy, this is encapsulated in double-membrane vesicles termed autophagosomes, which form from precursors referred to phagophores. Phagophores grow lipid influx endoplasmic reticulum into Atg9-positive compartments and local synthesis provides lipids for their expansion. How phagophore nucleation expansion are coordinated with unclear. Here, we show that Faa1, an enzyme activating fatty acids, recruited Atg9 directly binding negatively charged membranes preference phosphoinositides such PI3P PI4P. We define membrane-binding surface Faa1 its direct interaction membrane required recruitment Furthermore, physiological localization key efficient catalysis promotes Our results suggest positive feedback loop coupling synthesis.
Language: Английский
Citations
2
Autophagy Reports, Journal Year: 2024, Volume and Issue: 3(1)
Published: May 30, 2024
Language: Английский
Citations
0
Genetics, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 13, 2024
Abstract The endosomal sorting complex required for transport (ESCRT)-III is involved in membrane remodeling and abscission during intraluminal vesicle (ILV) formation at endosomes. Our data now suggest that ESCRT-III function could be connected to lipid of the membrane. This notion based on our finding proteins bind yeast serine incorporator (SERINC) homolog Tms1. Human SERINC3 SERINC5 are HIV-1 restriction factors have been shown act as scramblases, flipping phospholipids between leaflets. Due extraordinarily high sequence conservation Tms1 human SERINCs, it likely also a scramblase. While deletion TMS1 had only moderate effect multivesicular body (MVB) cargo proteins, simultaneous component Vps55/Vps68 led strong synergistic phenotype. pronounced synergism suggests perform parallel loosely resembles its overall structure. Thus, possible Since both Vps55 physically interact with we propose recruitment scramblase plays crucial role ESCRT-III-dependent
Language: Английский
Citations
0
Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(4)
Published: Feb. 15, 2024
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping researchers promote themselves alongside their papers. Alex van Vliet author on ‘ Exploring ATG9A interactome uncovers interaction VPS13A’, JCS. conducted research described this article while Postdoctoral Training Fellow Sharon Tooze's lab at The Francis Crick Institute, London, UK. He now an MRC Postdoc Sean Munro Laboratory Molecular Biology, Cambridge, UK, investigating mechanisms membrane trafficking.
Language: Английский
Citations
0