ArticleAutophagy2020
Mammalian Atg8-family proteins are upstream regulators of the lysosomalsystem by controlling MTOR and TFEB.
Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- ATG16L1 controls mammalian vacuolar proton ATPase.The Journal of cell biology · 2025Article
- BAK knockdown delays bleaching and alleviates oxidative DNA damage in a reef-building coral.Communications biology · 2025Article
- EGb761 suppressed vascular dementia via modulating Wnt/β-catenin signaling pathway-induced apoptosis and autophagy in hippocampal neuronal cells.European journal of medical research · 2025Article
- Exploring the multilayered response of TB bacterium Mycobacterial tuberculosis to lysosomal injury.FEMS microbiology reviews · 2025Review
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries.Journal of translational medicine · 2023Article
- Identification of Hub Genes and Typing of Tuberculosis Infections Based on Autophagy-Related Genes.Polish journal of microbiology · 2023Article
- Whole-Blood 3-Gene Signature as a Decision Aid for Rifapentine-based Tuberculosis Preventive Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- The multifaceted role of autophagy in cancer.The EMBO journal · 2022Review
- Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival.Communications biology · 2022Article
- Caffeine Inhibits Activation of the NLRP3 Inflammasome via Autophagy to Attenuate Microglia-Mediated Neuroinflammation in Experimental Autoimmune Encephalomyelitis.Journal of molecular neuroscience : MN · 2022Article
- Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Hepatocellular Carcinoma Based on Immunoscore Classification of Tumor.Journal of oncology · 2021Article
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11 authors at 5 institutions in 4 countries.
Funding
Abstract
Macroautophagy/autophagy delivers cytoplasmic cargo to lysosomes for degradation. In yeast, the single Atg8 protein plays a role in the formation of autophagosomes whereas in mammalian cells there are five to seven paralogs, referred to as mammalian Atg8s (mAtg8s: GABARAP, GABARAPL1, GABARAPL2, LC3A, LC3B, LC3B2 and LC3C) with incompletely defined functions. Here we show that a subset of mAtg8s directly control lysosomal biogenesis. This occurs at the level of TFEB, the principal regulator of the lysosomal transcriptional program. mAtg8s promote TFEB's nuclear translocation in response to stimuli such as starvation. GABARAP interacts directly with TFEB, whereas RNA-Seq analyses reveal that knockout of six genes encoding mAtg8s, or a triple knockout of the genes encoding all GABARAPs, diminishes the TFEB transcriptional program. We furthermore show that GABARAPs in cooperation with other proteins, IRGM, a factor implicated in tuberculosis and Crohn disease, and STX17, are required during starvation for optimal inhibition of MTOR, an upstream kinase of TFEB, and activation of the PPP3/calcineurin phosphatase that dephosphorylates TFEB, thus promoting its nuclear translocation. In conclusion, mAtg8s, IRGM and STX17 control lysosomal biogenesis by their combined or individual effects on MTOR, TFEB, and PPP3/calcineurin, independently of their roles in the formation of autophagosomal membranes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.