Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • 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 Article has an altmetric score of 26

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).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Blogged by 1
Posted by 27 X users
Referenced in 1 patents
On 2 Facebook pages
149 readers on Mendeley
See more details