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We assessed lung tissue mitochondrial bioenergetics in rats with tolerance (H-T) or susceptibility (H-S) to hyperoxia-induced ARDS. Results from studies in isolated mitochondria, tissue homogenate, and isolated perfused lungs show that mitochondrial bioenergetics are differentially altered in H-T and H-S lungs suggesting a potential role for mitochondrial bioenergetics in hyperoxia-induced ARDS. Results are clinically relevant since hyperoxia exposure is a primary therapy for patients with ARDS, and differential sensitivity to hyperoxia surely occurs in humans.
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This content will become publicly available on September 1, 2027
Computational modeling of substrate-dependent lung mitochondrial respiration and bioenergetics in rats with different susceptibility to hyperoxia-induced ARDS
We developed a comprehensive computational model of lung mitochondrial bioenergetics that integrates key regulatory mechanisms. The model, parameterized using respirometry data from lung mitochondria of hyperoxia-tolerant and -susceptible rats, identified adenine nucleotide translocase, cytochrome c oxidase, and proton leak as critical determinants of lung mitochondrial bioenergetic homeostasis. Model simulations predict that deficits in these processes drive rapid bioenergetic failure in the lungs of hyperoxia-susceptible rats.
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- Award ID(s):
- 2153387
- PAR ID:
- 10711376
- Publisher / Repository:
- American Physiological Society
- Date Published:
- Journal Name:
- American Journal of Physiology-Cell Physiology
- Volume:
- 331
- Issue:
- 3
- ISSN:
- 0363-6143
- Page Range / eLocation ID:
- C759 to C782
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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