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| http://dx.doi.org/10.1242/jcs.031773 | DOI Listing |
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Alzheimers Dement
December 2024
University of Pennsylvania, Philadelphia, PA, USA.
Background: Alzheimer's disease (AD) is neurodegenerative disease brought on by a combination of changes in multiple pathways that conglomerate to promote disease progression. AD often occurs alongside comorbid diseases, most often immune or vascular in nature, which have been shown to further increase AD risk. We previously showed that known AD variants also associate with secondary diseases in these categories, including rheumatoid arthritis, ischemic myocardial infarction, and both Type 1 and Type 2 diabetes.
View Article and Find Full Text PDFOscillatory autophagy induction is enabled by an updated AMPK-ULK1 regulatory wiring.
PLoS One
December 2024
Department of Genetics, ELTE Eötvös Loránd University, Budapest, Hungary.
Autophagy-dependent survival relies on a crucial oscillatory response during cellular stress. Although oscillatory behaviour is typically associated with processes like the cell cycle or circadian rhythm, emerging experimental and theoretical evidence suggests that such periodic dynamics may explain conflicting experimental results in autophagy research. In this study, we demonstrate that oscillatory behaviour in the regulation of the non-selective, stress-induced macroautophagy arises from a series of interlinked negative and positive feedback loops within the mTORC1-AMPK-ULK1 regulatory triangle.
View Article and Find Full Text PDFDynamic mitophagy trajectories hallmark brain aging.
Autophagy
December 2024
Translational Stem Cell Biology and Metabolism Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Studies using mitophagy reporter mice have established steady-state landscapes of mitochondrial destruction in mammalian tissues, sparking intense interest in basal mitophagy. Yet how basal mitophagy is modified by healthy aging in diverse brain cell types has remained a mystery. We present a comprehensive spatiotemporal analysis of mitophagy and macroautophagy dynamics in the aging mammalian brain, reporting critical region- and cell-specific turnover trajectories in a longitudinal study.
View Article and Find Full Text PDFFunctional omics of ORP7 in primary endothelial cells.
BMC Biol
December 2024
Minerva Foundation Institute for Medical Research, Tukholmankatu 8, 00290, Helsinki, Finland.
Background: Many members of the oxysterol-binding protein-related protein (ORP) family have been characterized in detail over the past decades, but the lipid transport and other functions of ORP7 still remain elusive. What is known about ORP7 points toward an endoplasmic reticulum and plasma membrane-localized protein, which also interacts with GABA type A receptor-associated protein like 2 (GABARAPL2) and unlipidated Microtubule-associated proteins 1A/1B light chain 3B (LC3B), suggesting a further autophagosomal/lysosomal association. Functional roles of ORP7 have been suggested in cholesterol efflux, hypercholesterolemia, and macroautophagy.
View Article and Find Full Text PDFBlocking autophagosome closure manifests the roles of mammalian Atg8-family proteins in phagophore formation and expansion during nutrient starvation.
Autophagy
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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