ArticleCell reports2021
SAC1 regulates autophagosomal phosphatidylinositol-4-phosphate for xenophagy-directed bacterial clearance.
Article in Cell reports, 2021. 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, 24 citations in OpenAlex.
- Phosphatidylinositol 4-kinase as a target of pathogens-friend or foe?FEBS letters · 2026Review
- Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis.Cell research · 2025Article
- Article
- Inducible antibacterial responses in macrophages.Nature reviews. Immunology · 2025Review
- Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.American journal of physiology. Renal physiology · 2024Article
- FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma.Nature communications · 2024Article
- Molecular Modulators and Receptors of Selective Autophagy: Disease Implication and Identification Strategies.International journal of biological sciences · 2024Review
- PtdIns4P exchange at endoplasmic reticulum-autolysosome contacts is essential for autophagy and neuronal homeostasis.Autophagy · 2023Article
- Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways.Cell & bioscience · 2023Article
- A detailed molecular network map and model of the NLRP3 inflammasome.Frontiers in immunology · 2023Review
- Innate host defense mechanisms SAC bacteria by regulating phosphoinositide kinases and phosphatases.Autophagy · 2022Article
- Perturbation of ATG16L1 function impairs the biogenesis of Salmonella and Coxiella replication vacuoles.Molecular microbiology · 2022Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphoinositides are important molecules in lipid signaling, membrane identity, and trafficking that are spatiotemporally controlled by factors from both mammalian cells and intracellular pathogens. Here, using small interfering RNA (siRNA) directed against phosphoinositide kinases and phosphatases, we screen for regulators of the host innate defense response to intracellular bacterial replication. We identify SAC1, a transmembrane phosphoinositide phosphatase, as an essential regulator of xenophagy. Depletion or inactivation of SAC1 compromises fusion between Salmonella-containing autophagosomes and lysosomes, leading to increased bacterial replication. Mechanistically, the loss of SAC1 results in aberrant accumulation of phosphatidylinositol-4-phosphate [PI(4)P] on Salmonella-containing autophagosomes, thus facilitating recruitment of SteA, a PI(4)P-binding Salmonella effector protein, which impedes lysosomal fusion. Replication of Salmonella lacking SteA is suppressed by SAC-1-deficient cells, however, demonstrating bacterial adaptation to xenophagy. Our findings uncover a paradigm in which a host protein regulates the level of its substrate and impairs the function of a bacterial effector during xenophagy.
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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.