Document Type
Article
Publication Date
5-25-2021
Publication Title
Nature Communications
Volume
12
Issue
1
First page number:
1
Last page number:
19
Abstract
The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.
Disciplines
Neuroscience and Neurobiology
File Format
File Size
2751 KB
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Marutani, E.,
Morita, M.,
Hirai, S.,
Kai, S.,
Grange, R.,
Miyazaki, Y.,
Nagashima, F.,
Traeger, L.,
Magliocca, A.,
Ida, T.,
Matsunaga, T.,
Flicker, D.,
Corman, B.,
Mori, N.,
Yamazaki, Y.,
Batten, A.,
Li, R.,
Tanaka, T.,
Ikeda, T.,
Nakagawa, A.,
Atochin, D.,
Ihara, H.,
Olenchock, B.,
Shen, X.,
Nishida, M.,
Hanaoka, K.,
Kevil, C.,
Xian, M.,
Bloch, D. B.,
Akaike, T.,
Hindle, A. G.
(2021).
Sulfide Catabolism Ameliorates Hypoxic Brain Injury.
Nature Communications, 12(1),
1-19.
http://dx.doi.org/10.1038/s41467-021-23363-x