ArticleNature medicine2010
Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 146 citations in OpenAlex.
- LINE-1 retrotransposition modulates metabolic stress and promotes cuproptosis resistance in lung squamous cell carcinoma by disrupting mitochondrial membrane homeostasis.Journal of translational medicine · 2026Article
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.Molecular neurobiology · 2025Review
- Magnitude of obesity alone does not alter the alveolar lipidome.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Activation and substrate specificity of the human P4-ATPase ATP8B1.Nature communications · 2023Article
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- Super-swelling behavior of stacked lipid bilayer systems.The European physical journal. E, Soft matter · 2023Article
- Study on the relationship between selenium and cadmium in diseased human lungs.Advances in redox research · 2023Article
- Advances in methods to analyse cardiolipin and their clinical applications.Trends in analytical chemistry : TRAC · 2022Article
- Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.Cell death & disease · 2022Article
- De novo labeling and trafficking of individual lipid species in live cells.Molecular metabolism · 2022Article
- Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes.Biophysical journal · 2022Article
- Redox Activation of Mitochondrial DAMPs and the Metabolic Consequences for Development of Autoimmunity.Antioxidants & redox signaling · 2022Review
- Matrix Metalloproteinase 7 Expression and Apical Epithelial Defects inBiomolecules · 2022Article
- Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies.World journal of hepatology · 2022Review
- AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy.Autophagy · 2021Article
- Lipid flippases as key players in plant adaptation to their environment.Nature plants · 2021Review
- Pulmonary lipid modulation: A possible therapeutic target for SARS-CoV-2 infection.Medical hypotheses · 2021Article
28 more citing papers are in PubMed but not listed here.
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22 authors at 3 institutions in 1 country.
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Abstract
Pneumonia remains the leading cause of death from infection in the US, yet fundamentally new conceptual models underlying its pathogenesis have not emerged. We show that humans and mice with bacterial pneumonia have markedly elevated amounts of cardiolipin, a rare, mitochondrial-specific phospholipid, in lung fluid and find that it potently disrupts surfactant function. Intratracheal cardiolipin administration in mice recapitulates the clinical phenotype of pneumonia, including impaired lung mechanics, modulation of cell survival and cytokine networks and lung consolidation. We have identified and characterized the activity of a unique cardiolipin transporter, the P-type ATPase transmembrane lipid pump Atp8b1, a mutant version of which is associated with severe pneumonia in humans and mice. Atp8b1 bound and internalized cardiolipin from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene transfer in mice lessened bacteria-induced lung injury and improved survival. The results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective. This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia.
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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.