粒体自噬
品脱1
细胞生物学
造血
干细胞
祖细胞
线粒体
生物
帕金
造血干细胞
细胞凋亡
自噬
生物化学
病理
医学
疾病
帕金森病
作者
Koichi Murakami,Daisuke Kurotaki,Wataru Kawase,Shunsuke Soma,Yumi Fukuchi,Hiroyoshi Kunimoto,Ryusuke Yoshimi,Shuhei Koide,Motohiko Oshima,Takako Hishiki,Noriyo Hayakawa,Tomomi Matsuura,Mayumi Oda,Kiichi Yanagisawa,Hiroshi Kobayashi,Miho Haraguchi,Yoshitoshi Atobe,Kengo Funakoshi,Atsushi Iwama,Keiyo Takubo,Shinichiro Okamoto,Tomohide Tamura,Hideaki Nakajima
出处
期刊:Cell Reports
[Elsevier]
日期:2021-01-01
卷期号:34 (1): 108579-108579
被引量:28
标识
DOI:10.1016/j.celrep.2020.108579
摘要
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is a unique enzyme introducing O-GlcNAc moiety on target proteins, and it critically regulates various cellular processes in diverse cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) remain elusive. Here, using Ogt conditional knockout mice, we show that OGT is essential for HSPCs. Ogt is highly expressed in HSPCs, and its disruption induces rapid loss of HSPCs with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient hematopoietic stem cells (HSCs) lose quiescence, cannot be maintained in vivo, and become vulnerable to regenerative and competitive stress. Interestingly, Ogt-deficient HSCs accumulate defective mitochondria due to impaired mitophagy with decreased key mitophagy regulator, Pink1, through dysregulation of H3K4me3. Furthermore, overexpression of PINK1 restores mitophagy and the number of Ogt-deficient HSCs. Collectively, our results reveal that OGT critically regulates maintenance and stress response of HSCs by ensuring mitochondrial quality through PINK1-dependent mitophagy.
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