ArticleNature communications2021
Sulfide catabolism ameliorates hypoxic brain injury.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70citing papers in PubMed
11.6field-weighted citation impact, top 1% of its field
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Who cites it
70 citing papers in PubMed, 135 citations in OpenAlex.
- Impact-acceleration head injury results in optic neuropathy in the thirteen-lined ground squirrel.Communications biology · 2026Article
- Reactive sulfur species are inactivated and excreted as trimethylsulfonium ion by thiopurine S-methyltransferase.Redox biology · 2026Article
- CoQExperimental & molecular medicine · 2026Review
- Candidate Mechanisms of Cerebral Ischemia/Hypoxia Tolerance: Insights from Hibernating Rodents.Neurochemical research · 2026Review
- Sulfide:quinone oxidoreductase drives mitochondrial supersulfide metabolism to regulate bioenergetics and longevity in eukaryotes.bioRxiv : the preprint server for biology · 2026Article
- Multifaceted roles for persulfide species in redox chemical biology.Nature chemical biology · 2026Review
- Hydrogen sulfide increases intracellular oxygen and inhibits the HIF response.The Journal of biological chemistry · 2026Article
- Intratumoral microbiome evaluated progression and outcome of patients with HBV-associated hepatocellular carcinoma.Discover oncology · 2026Article
- Role of Sulfide Quinone Oxidoreductase and Supersulfides in Hepatic Ischemia-Reperfusion Injury in Mice.Antioxidants (Basel, Switzerland) · 2026Article
- Hydrogen Sulfide Consumption and Cell Bioenergetics in Human (Patho)physiology.Handbook of experimental pharmacology · 2026Review
- Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.Handbook of experimental pharmacology · 2026Review
- Enriched Environment Ameliorates Cerebral Ischemia-Reperfusion Injury via Dopamine-HAntioxidants (Basel, Switzerland) · 2025Article
- Power and poison: The intersections of HThe Journal of biological chemistry · 2025Review
- Sulfite oxidase deficiency causes persulfidation loss and hydrogen sulfide release.The Journal of clinical investigation · 2025Article
- Hydrogen sulfide inhibits recruitment of monocyte-derived tumor associated macrophages in glioblastoma by downregulating CXCL12.Redox biology · 2025Article
- Hydrogen sulfide/polysulfides signaling and neuronal diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Sulfide Quinone Oxidoreductase Alleviates Acute Ulcerative Colitis by Regulating Mitochondrial Dysfunction.MedComm · 2025Article
- Gut sulfide metabolism modulates behavior and brain bioenergetics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Knockout of the sulfide: quinone oxidoreductase SQR reduces growth of HCT116 tumor xenograft.Redox biology · 2025Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 13 institutions in 2 countries.
Eizo Marutani *Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Masanobu Morita *Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Shuichi Hirai *Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Shinichi KaiAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1804-3071
Robert M H GrangeAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Yusuke MiyazakiAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Fumiaki NagashimaAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Lisa TraegerAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Aurora MaglioccaAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Tomoaki IdaDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Tetsuro MatsunagaDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Daniel R FlickerDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Benjamin CormanAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Naohiro MoriAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Yumiko YamazakiAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Annabelle BattenAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Rebecca LiAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1567-9541
Tomohiro TanakaDivision of Cardiocirculatory Signaling, National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems & Center for Novel Science Initiatives, National Institutes of Natural Sciences, Okazaki, Japan.ORCID 0000-0001-7442-4912
Takamitsu IkedaAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1245-2958
Akito NakagawaAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Dmitriy N AtochinHarvard Medical School, Boston, MA, USA.
Hideshi IharaDepartment of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka, Japan.ORCID 0000-0002-8971-5138
Benjamin A OlenchockHarvard Medical School, Boston, MA, USA.
Xinggui ShenDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Motohiro NishidaDivision of Cardiocirculatory Signaling, National Institute for Physiological Sciences & Exploratory Research Center on Life and Living Systems & Center for Novel Science Initiatives, National Institutes of Natural Sciences, Okazaki, Japan.ORCID 0000-0002-2587-5458
Kenjiro HanaokaGraduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.ORCID 0000-0003-0797-4038
Christopher G KevilDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID 0000-0003-0863-7260
Ming XianDepartment of Chemistry, Brown University, Providence, RI, USA.
Donald B BlochAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Takaaki AkaikeDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Allyson G HindleAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1983-9573
Hozumi MotohashiDepartment of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. hozumim@med.tohoku.ac.jp.ORCID 0000-0002-7261-1033
Fumito IchinoseAnesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. fichinose@mgh.harvard.edu.ORCID 0000-0003-4535-1632
Harvard University · USMassachusetts General Hospital · USTohoku University · JPLouisiana State University Health Sciences Center Shreveport · USBrigham and Women's Hospital · USBroad Institute · USBrown University · USKyushu University · JPNational Institutes of Natural Sciences · JPOsaka Prefecture University · JPThe University of Tokyo · JPTohoku Institute of Technology · JPUniversity of Nevada, Las Vegas · US
Funding
Stress Exacerbates Myocardial Ischemic Injury by Blocking Estrogen's Antidoxidant Protection in the Female HeartP20GM121307 · NIGMS · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Christopher G Kevil · 2018 to 2026
$23.6MIMPACT OF HYDROGEN SULFIDE ON OUTCOME OF CARDIAC ARREST AND CARDIOPULMONARY RESUSR01HL101930 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ICHINOSE, FUMITO · 2010 to 2014
$2.1MHydrogen sulfide and vascular remodelingR01HL113303 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI KEVIL, CHRISTOPHER G · 2012 to 2016
$1.8McGMP-dependent protein kinase I as a new target against strokeR01NS096237 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ATOCHIN, DMITRIY · 2016 to 2020
$1.8MRole of sulfide catabolism in ischemic brain injuryR01NS112373 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ICHINOSE, FUMITO · 2019 to 2023
$1.7MCSE regulation of vascular remodelingR01HL149264 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI KEVIL, CHRISTOPHER G · 2020 to 2023
$1.7MNovel Antidotes for H2S PoisoningR21NS116671 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ICHINOSE, FUMITO, XIAN, MING · 2020 to 2021
$437kHoward Hughes Medical InstituteNHLBI NIH HHS R01 HL101930NHLBI NIH HHS R01 HL113303NHLBI NIH HHS R01 HL149264NIGMS NIH HHS P20 GM121307NINDS NIH HHS R01 NS096237NINDS NIH HHS R01 NS112373NINDS NIH HHS R21 NS116671
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.
Indexed as
AnimalsBrainBrain InjuriesCells, CulturedFemaleHydrogen SulfideHypoxiaMaleMembrane Potential, MitochondrialMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutMitochondriaNADQuinone ReductasesHydrogen SulfideNADQuinone Reductasessulfide quinone reductase
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