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Contribution of NRF2 to sulfur metabolism and mitochondrial activity.
Alam, Md Morshedul; Kishino, Akihiro; Sung, Eunkyu; Sekine, Hiroki; Abe, Takaaki; Murakami, Shohei; Akaike, Takaaki; Motohashi, Hozumi.
Afiliación
  • Alam MM; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan; Department of Genetic Engineering and Biotechnology, Bangabandhu Sheikh Mujibur Rahman Maritime University, Mirpur 12, Dhaka, 1216, Bangladesh.
  • Kishino A; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
  • Sung E; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
  • Sekine H; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
  • Abe T; Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
  • Murakami S; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
  • Akaike T; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan. Electronic address: takaike@med.tohoku.ac.jp.
  • Motohashi H; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan. Electronic address: hozumim@med.tohoku.ac.jp.
Redox Biol ; 60: 102624, 2023 04.
Article en En | MEDLINE | ID: mdl-36758466
NF-E2-related factor 2 (NRF2) plays a crucial role in the maintenance of cellular homeostasis by regulating various enzymes and proteins that are involved in the redox reactions utilizing sulfur. While substantial impacts of NRF2 on mitochondrial activity have been described, the precise mechanism by which NRF2 regulates mitochondrial function is still not fully understood. Here, we demonstrated that NRF2 increased intracellular persulfides by upregulating the cystine transporter xCT encoded by Slc7a11, a well-known NRF2 target gene. Persulfides have been shown to play an important role in mitochondrial function. Supplementation with glutathione trisulfide (GSSSG), which is a form of persulfide, elevated the mitochondrial membrane potential (MMP), increased the oxygen consumption rate (OCR) and promoted ATP production. Persulfide-mediated mitochondrial activation was shown to require the mitochondrial sulfur oxidation pathway, especially sulfide quinone oxidoreductase (SQOR). Consistently, NRF2-mediated mitochondrial activation was also dependent on SQOR activity. This study clarified that the facilitation of persulfide production and sulfur metabolism in mitochondria by increasing cysteine availability is one of the mechanisms for NRF2-dependent mitochondrial activation.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Sulfuros / Factor 2 Relacionado con NF-E2 Idioma: En Revista: Redox Biol Año: 2023 Tipo del documento: Article País de afiliación: Bangladesh

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Sulfuros / Factor 2 Relacionado con NF-E2 Idioma: En Revista: Redox Biol Año: 2023 Tipo del documento: Article País de afiliación: Bangladesh