Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Autor:	Zhou C; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Kuang M; Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China., Tao Y; Department of Gynecology, The affiliated ZhuZhou Hospital (ZhuZhou Central Hospital), Xiangya Medical College of Central South University, Zhuzhou, Hunan 412007, China., Wang J; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Luo Y; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Fu Y; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Chen Z; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Liu Y; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Li Z; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Wu W; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China., Wang L; Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, Chongqing 400016, China., Dou Y; Department of Hematology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. Electronic address: douying523@aliyun.com., Wang J; State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: wangjunping@tmmu.edu.cn., Hou Y; Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Department of Hematology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University, Chongqing 400016, China. Electronic address: houyu@cqmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Sep 05; Vol. 31 (9), pp. 1359-1375.e8. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1016/j.stem.2024.06.007
Abstrakt:	Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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