Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-23363-x
Keywords
-
Categories
Funding
- Ministry of Education, Sciences, Sports, and Technology (MEXT), Japan [19K07341, 20K07306, 19K07554, 18H05277]
- CREST
- Japan Science and Technology Agency (JST) [JPMJCR2024]
- Japan Agency for Medical Research and Development (AMED) [JP21gm5010002]
- National Institute of Neurological Disorders and Stroke (NINDS) [R01NS096237, R21NS116671]
- National Heart, Lung, and Blood Institute (NHLBI) [R01HL113303, R01HL149264, R01HL101930]
- National Institute of General Medical Science (NIGMS) [P20GM121307]
- National Science Foundation [1929592]
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [1929592] Funding Source: National Science Foundation
- Grants-in-Aid for Scientific Research [20K07306, 19K07341, 19K07554, 18H05277] Funding Source: KAKEN
Ask authors/readers for more resources
The sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and its capacity to catabolize sulfide in mice, rats, and naturally hypoxia-tolerant ground squirrels. Silencing SQOR increased brain sensitivity to hypoxia, while neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation and ischemic brain injury. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia, indicating a potential therapeutic target for ischemic brain injury.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available