Atg1 phosphoregulates different steps and factors in autophagy. Schreiber et al. report in Molecular Cell on the cell-free identification of a negative feedback ejection of Atg1 from the pre-autophagosomal structure (PAS), followed by positive feedback recruitment of Atg1 to phagophore-resident Atg8-PE, followed by yet another, negative feedback inhibition of the Atg8 conjugation machinery.
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http://dx.doi.org/10.1016/j.tcb.2021.12.005 | DOI Listing |
Cells
January 2025
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, Japan.
The autophagy-related ubiquitin-like conjugation systems, the ATG8 and ATG12 systems, are universally conserved in eukaryotes. However, the covalent bond in the ATG12 system has recently been shown to be evolutionarily lost in Apicomplexa. Here, we show that all genes associated with the ATG12 system are absent in piroplasmida, a lineage within Apicomplexa.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Instituto de Investigaciones Biomédicas Sols-Morreale CSIC-UAM, 28029 Madrid, Spain. Electronic address:
A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipidation. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Mutations that increase LRRK2 kinase activity have been linked to Parkinson's disease and Crohn's disease. LRRK2 is also activated by lysosome damage. However, the endogenous cellular mechanisms that control LRRK2 kinase activity are not well understood.
View Article and Find Full Text PDFmBio
December 2024
Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, India.
parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components.
View Article and Find Full Text PDFAutophagy
December 2024
Division of Pediatric Hematology and Oncology, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Macroautophagy/autophagy, an evolutionarily conserved cellular degradation pathway, involves phagophores that sequester cytoplasmic constituents and mature into autophagosomes for subsequent lysosomal delivery. The gene family, comprising the and subfamilies in mammals, encodes ubiquitin-like proteins that are conjugated to phagophore membranes during autophagosome biogenesis. A central question in the field is how Atg8-family proteins are precisely involved in autophagosome formation, which remains controversial and challenging, at least in part due to the short lifespan of phagophores.
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