ArticlePloS one2019
PINK1 attenuates mtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
80 citing papers in PubMed, 99 citations in OpenAlex.
- A Systems View of Posterior Capsule Opacification: TGF-β/ROS Signaling, Mitochondrial Homeostasis, and Injury/Aging Cues-Therapeutic Opportunities.Investigative ophthalmology & visual science · 2026Review
- Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Neuropsychiatric disorders in pulmonary fibrosis: from brain network alterations to inflammatory mechanisms and therapeutic implications.Journal of neuroinflammation · 2026Review
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Mitophagy in kidney and lung epithelial cells: molecular mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Mitophagy in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- MIF/CD74 axis regulates alveolar epithelial type II cell apoptosis, autophagy, and transdifferentiation in bronchopulmonary dysplasia via the TGFβ1/SMAD4 pathway.Respiratory research · 2025Article
- Cyclic GMP-AMP synthase expression is enhanced in systemic sclerosis-associated interstitial lung disease and stimulates inflammatory myofibroblast activation.The European respiratory journal · 2025Article
- GSR Deficiency Exacerbates Oxidative Stress and Promotes Pulmonary Fibrosis.Biomolecules · 2025Article
- Mechanisms and markers of lung ageing in health and disease.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell.Advanced biology · 2025Review
- Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand.International journal of molecular sciences · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
We have previously shown that endoplasmic reticulum stress (ER stress) represses the PTEN inducible kinase 1 (PINK1) in lung type II alveolar epithelial cells (AECII) reducing mitophagy and increasing the susceptibility to lung fibrosis. Although increased circulating mitochondrial DNA (mtDNA) has been reported in chronic lung diseases, the contribution of mitophagy in the modulation of mitochondrial DAMP release and activation of profibrotic responses is unknown. In this study, we show that ER stress and PINK1 deficiency in AECII led to mitochondrial stress with significant oxidation and damage of mtDNA and subsequent extracellular release. Extracellular mtDNA was recognized by TLR9 in AECII by an endocytic-dependent pathway. PINK1 deficiency-dependent mtDNA release promoted activation of TLR9 and triggered secretion of the profibrotic factor TGF-β which was rescued by PINK1 overexpression. Enhanced mtDNA oxidation and damage were found in aging and IPF human lungs and, in concordance, levels of circulating mtDNA were significantly elevated in plasma and bronchoalveolar lavage (BAL) from patients with IPF. Free mtDNA was found elevated in other ILDs with low expression of PINK1 including hypersensitivity pneumonitis and autoimmune interstitial lung diseases. These results support a role for PINK1 mediated mitophagy in the attenuation of mitochondrial damage associated molecular patterns (DAMP) release and control of TGF-β mediated profibrotic responses.
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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.