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Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome.

Publication ,  Conference
Kraft, BD; Pavlisko, EN; Roggli, VL; Piantadosi, CA; Suliman, HB
Published in: Lab Invest
September 2023

Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure and death in patients in the intensive care unit. Experimentally, acute lung injury resolution depends on the repair of mitochondrial oxidant damage by the mitochondrial quality control (MQC) pathways, mitochondrial biogenesis, and mitophagy, but nothing is known about this in the human lung. In a case-control autopsy study, we compared the lungs of subjects dying of ARDS (n = 8; cases) and age-/gender-matched subjects dying of nonpulmonary causes (n = 7; controls). Slides were examined by light microscopy and immunofluorescence confocal microscopy, randomly probing for co-localization of citrate synthase with markers of oxidant stress, mitochondrial DNA damage, mitophagy, and mitochondrial biogenesis. ARDS lungs showed diffuse alveolar damage with edema, hyaline membranes, and neutrophils. Compared with controls, a high degree of mitochondrial oxidant damage was seen in type 2 epithelial (AT2) cells and alveolar macrophages by 8-hydroxydeoxyguanosine and malondialdehyde co-staining with citrate synthase. In ARDS, antioxidant protein heme oxygenase-1 and DNA repair enzyme N-glycosylase/DNA lyase (Ogg1) were found in alveolar macrophages but not in AT2 cells. Moreover, MAP1 light chain-3 (LC3) and serine/threonine-protein kinase (Pink1) staining were absent in AT2 cells, suggesting a mitophagy failure. Nuclear respiratory factor-1 staining was missing in the alveolar region, suggesting impaired mitochondrial biogenesis. Widespread hyperproliferation of AT2 cells in ARDS could suggest defective differentiation into type 1 cells. ARDS lungs show profuse mitochondrial oxidant DNA damage but little evidence of MQC activity in AT2 epithelium. Because these pathways are important for acute lung injury resolution, our findings support MQC as a novel pharmacologic target for ARDS resolution.

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Published In

Lab Invest

DOI

EISSN

1530-0307

Publication Date

September 2023

Volume

103

Issue

9

Start / End Page

100197

Location

United States

Related Subject Headings

  • Respiratory Distress Syndrome
  • Pathology
  • Oxidants
  • Lung
  • Humans
  • Citrate (si)-Synthase
  • Acute Lung Injury
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Kraft, B. D., Pavlisko, E. N., Roggli, V. L., Piantadosi, C. A., & Suliman, H. B. (2023). Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome. In Lab Invest (Vol. 103, p. 100197). United States. https://doi.org/10.1016/j.labinv.2023.100197
Kraft, Bryan D., Elizabeth N. Pavlisko, Victor L. Roggli, Claude A. Piantadosi, and Hagir B. Suliman. “Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome.” In Lab Invest, 103:100197, 2023. https://doi.org/10.1016/j.labinv.2023.100197.
Kraft BD, Pavlisko EN, Roggli VL, Piantadosi CA, Suliman HB. Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome. In: Lab Invest. 2023. p. 100197.
Kraft, Bryan D., et al. “Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome.Lab Invest, vol. 103, no. 9, 2023, p. 100197. Pubmed, doi:10.1016/j.labinv.2023.100197.
Kraft BD, Pavlisko EN, Roggli VL, Piantadosi CA, Suliman HB. Alveolar Mitochondrial Quality Control During Acute Respiratory Distress Syndrome. Lab Invest. 2023. p. 100197.

Published In

Lab Invest

DOI

EISSN

1530-0307

Publication Date

September 2023

Volume

103

Issue

9

Start / End Page

100197

Location

United States

Related Subject Headings

  • Respiratory Distress Syndrome
  • Pathology
  • Oxidants
  • Lung
  • Humans
  • Citrate (si)-Synthase
  • Acute Lung Injury
  • 3202 Clinical sciences
  • 1103 Clinical Sciences