ArticleCellular and molecular life sciences : CMLS2019
Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4.
Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Bacterial lipid structural diversity mediates commensalism and pathogenesis.Nature reviews. Microbiology · 2026Review
- Saturated cardiolipins are potent disruptors of inner mitochondrial membrane structure and function.bioRxiv : the preprint server for biology · 2026Article
- Clotting the Gap Between Mitochondria-Mediated Immunity and Mitochondrial Transfer.Circulation research · 2026Review
- Bioengineered Bacterial Vesicles and Biomimetic Hybrids Eliminate Biofilms and Balance the Gut Microbiome.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- Phosphole-Based Fluorescent Biomaterials for Imaging and Therapy.Chemical & biomedical imaging · 2025Review
- Trimming the fat: a brief review of lipids at the host-pathogen interface.Infection and immunity · 2025Review
- The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.Molecular neurobiology · 2025Review
- Cockroach Microbiome Disrupts Indoor Environmental Microbial Ecology with Potential Public Health Implications.Environment & health (Washington, D.C.) · 2025Article
- Exploring the Effects of Incorporating Different Bioactive Phospholipids into Messenger Ribonucleic Acid Lipid Nanoparticle (mRNA LNP) Formulations.ACS bio & med chem Au · 2025Article
- Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Cardiolipin's multifaceted role in immune response: a focus on interacting proteins.Frontiers in immunology · 2025Review
- Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer-Membrane-Vesicle Vaccine.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Dictyophora indusiata polysaccharide mediates priming of the NLRP3 inflammasome activation via TLR4/ NF-κB signaling pathway to exert immunostimulatory effects.Journal of applied biomedicine · 2024Article
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Phosphatidylglycerol to Treat Chronic Skin Wounds in Diabetes.Pharmaceutics · 2023Review
- Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases.Frontiers in immunology · 2023Review
- Resolution Potential of Necrotic Cell Death Pathways.International journal of molecular sciences · 2022Review
- Activation of Toll-like receptor 4 by Ebola virus-shed glycoprotein is direct and requires the internal fusion loop but not glycosylation.Cell reports · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Cardiolipins (CLs) are tetra-acylated diphosphatidylglycerols found in bacteria, yeast, plants, and animals. In healthy mammals, CLs are unsaturated, whereas saturated CLs are found in blood cells from Barth syndrome patients and in some Gram-positive bacteria. Here, we show that unsaturated but not saturated CLs block LPS-induced NF-κB activation, TNF-α and IP-10 secretion in human and murine macrophages, as well as LPS-induced TNF-α and IL-1β release in human blood mononuclear cells. Using HEK293 cells transfected with Toll-like receptor 4 (TLR4) and its co-receptor Myeloid Differentiation 2 (MD2), we demonstrate that unsaturated CLs compete with LPS for binding TLR4/MD2 preventing its activation, whereas saturated CLs are TLR4/MD2 agonists. As a consequence, saturated CLs induce a pro-inflammatory response in macrophages characterized by TNF-α and IP-10 secretion, and activate the alternative NLRP3 inflammasome pathway in human blood-derived monocytes. Thus, we identify that double bonds discriminate between anti- and pro-inflammatory properties of tetra-acylated molecules, providing a rationale for the development of TLR4 activators and inhibitors for use as vaccine adjuvants or in the treatment of TLR4-related diseases.
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Registered trials
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.