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SDHAF1 confers metabolic resilience to aging hematopoietic stem cells by promoting mitochondrial ATP production.
Watanuki, Shintaro; Kobayashi, Hiroshi; Sugiura, Yuki; Yamamoto, Masamichi; Karigane, Daiki; Shiroshita, Kohei; Sorimachi, Yuriko; Morikawa, Takayuki; Fujita, Shinya; Shide, Kotaro; Haraguchi, Miho; Tamaki, Shinpei; Mikawa, Takumi; Kondoh, Hiroshi; Nakano, Hiroyasu; Sumiyama, Kenta; Nagamatsu, Go; Goda, Nobuhito; Okamoto, Shinichiro; Nakamura-Ishizu, Ayako; Shimoda, Kazuya; Suematsu, Makoto; Suda, Toshio; Takubo, Keiyo.
Afiliação
  • Watanuki S; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Kobayashi H; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Department of Cell Fate Biology and Stem Cell Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: hiroshi.kobayashi.b3@tohoku.a
  • Sugiura Y; Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan; Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
  • Yamamoto M; Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan.
  • Karigane D; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Shiroshita K; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Sorimachi Y; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Department of Life Sciences and Medical BioScience, Waseda University School of Advanced Science and Engineering, Tokyo 162-8480, Japan.
  • Morikawa T; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
  • Fujita S; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Shide K; Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • Haraguchi M; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
  • Tamaki S; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
  • Mikawa T; Geriatric Unit, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
  • Kondoh H; Geriatric Unit, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
  • Nakano H; Department of Biochemistry, Toho University School of Medicine, Tokyo 143-8540, Japan.
  • Sumiyama K; Laboratory of Animal Genetics and Breeding, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan; RIKEN Center for Biosystems Dynamics Research, Laboratory for Mouse Genetic Engineering, Osaka 565-0871, Japan.
  • Nagamatsu G; Center for Advanced Assisted Reproductive Technologies, University of Yamanashi, Kofu 400-8501, Japan.
  • Goda N; Department of Life Sciences and Medical BioScience, Waseda University School of Advanced Science and Engineering, Tokyo 162-8480, Japan.
  • Okamoto S; Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
  • Nakamura-Ishizu A; Department of Microscopic and Developmental Anatomy, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
  • Shimoda K; Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
  • Suematsu M; Department of Biochemistry, Keio University School of Medicine, Tokyo 160-8582, Japan; Live Imaging Center, Central Institute for Experimental Medicine and Life Science, Kawasaki 210-0821, Japan.
  • Suda T; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.
  • Takubo K; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Department of Cell Fate Biology and Stem Cell Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: keiyot@gmail.com.
Cell Stem Cell ; 31(8): 1145-1161.e15, 2024 Aug 01.
Article em En | MEDLINE | ID: mdl-38772377
ABSTRACT
Aging generally predisposes stem cells to functional decline, impairing tissue homeostasis. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival. High-resolution real-time ATP analysis with glucose tracing and metabolic flux analysis revealed that old HSCs reprogram their metabolism to activate the pentose phosphate pathway (PPP), becoming more resistant to oxidative stress and less dependent on glycolytic ATP production at steady state. As a result, old HSCs can survive without glycolysis, adapting to the physiological cytokine environment in bone marrow. Mechanistically, old HSCs enhance mitochondrial complex II metabolism during stress to promote ATP production. Furthermore, increased succinate dehydrogenase assembly factor 1 (SDHAF1) in old HSCs, induced by physiological low-concentration thrombopoietin (TPO) exposure, enables rapid mitochondrial ATP production upon metabolic stress, thereby improving survival. This study provides insight into the acquisition of resilience through metabolic reprogramming in old HSCs and its molecular basis to ameliorate age-related hematopoietic abnormalities.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Trifosfato de Adenosina / Mitocôndrias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Trifosfato de Adenosina / Mitocôndrias Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article