Redox Imbalance in Idiopathic Pulmonary Fibrosis: A Role for Oxidant Cross-Talk Between NADPH Oxidase Enzymes and Mitochondria

Carmen Veith, Agnes W. Boots, Musa Idris, Frederik-Jan van Schooten, Albert van der Vliet*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)
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Abstract

Recent Advances: IPF is characterized by increased production of reactive oxygen species (ROS), primarily by NADPH oxidases (NOXes) and mitochondria, as well as altered antioxidant defenses. Recent studies have identified the NOX isoform NOX4 as a key player in various important aspects of IPF pathology. In addition, mitochondrial dysfunction is thought to enhance pathological features of IPF, in part by increasing mitochondrial ROS (mtROS) production and altering cellular metabolism. Recent findings indicate reciprocal interactions between NOX enzymes and mitochondria, which affect regulation of NOX activity as well as mitochondrial function and mtROS production, and collectively promote epithelial injury and profibrotic signaling. Critical Issues and Future Directions: The precise molecular mechanisms by which ROS from NOX or mitochondria contribute to IPF pathology are not known. This review summarizes the current knowledge with respect to the various aspects of ROS imbalance in the context of IPF and its proposed roles in disease development, with specific emphasis on the importance of inappropriate NOX activation, mitochondrial dysfunction, and the emerging evidence of NOX-mitochondria cross-talk as important drivers in IPF pathobiology.

Original languageEnglish
Pages (from-to)1092-1115
Number of pages24
JournalAntioxidants & Redox Signaling
Volume31
Issue number14
Early online date5 Apr 2019
DOIs
Publication statusPublished - 10 Nov 2019

Keywords

  • IPF
  • reactive oxygen species
  • aging
  • lung
  • NOX4
  • mitochondria
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • GROWTH-FACTOR-BETA
  • INHALED N-ACETYLCYSTEINE
  • EXTRACELLULAR-SUPEROXIDE DISMUTASE
  • LOWER RESPIRATORY-TRACT
  • INDUCED LUNG INJURY
  • OXIDATIVE STRESS
  • REACTIVE OXYGEN
  • TGF-BETA
  • DNA-DAMAGE

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