Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis
Ana L. Mora, … , Marta Bueno, Mauricio Rojas
Ana L. Mora, … , Marta Bueno, Mauricio Rojas
Published February 1, 2017
Citation Information: J Clin Invest. 2017;127(2):405-414. https://doi.org/10.1172/JCI87440.
View: Text | PDF
Review

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

  • Text
  • PDF
Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients.

Authors

Ana L. Mora, Marta Bueno, Mauricio Rojas

×

Figure 1

Mitochondrial dysfunction and lung fibrosis.

Options: View larger image (or click on image) Download as PowerPoint
Mitochondrial dysfunction and lung fibrosis.
Aging and ER stress cause m...
Aging and ER stress cause mitochondrial dysfunction in type II alveolar epithelial cells (AECIIs) by diminishing the expression of the mitochondrial homeostasis regulator PINK1. Deficiency of PINK1 causes mitochondrial dysfunction, which is characterized by low activity of the electron transport chain (ETC) complexes I and IV, alterations in mtDNA metabolism, and insufficient mitophagy, leading to increased susceptibility to apoptosis and induction of TGF-β. TGF-β stimulation of lung fibroblasts has been shown to decrease PINK1 levels and promote insufficient mitophagy and myofibroblast differentiation. Additionally, aging and TGF-β stimulation reduce the expression of SIRT3. SIRT3 deficiency increases levels of acetylated (Ac) MnSOD and consequently increases mitochondrial ROS levels and mtDNA damage, which are also related to low expression of the DNA repair enzyme 8-oxoguanine-DNA glycosylase-1 (OGG1).
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts