OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy

被引：35

作者：

Murakami, Koichi ^{[1
,2
,3
]}

Kurotaki, Daisuke ^{[4
]}

Kawase, Wataru ^{[4
]}

Soma, Shunsuke ^{[1
]}

Fukuchi, Yumi ^{[1
]}

Kunimoto, Hiroyoshi ^{[2
]}

Yoshimi, Ryusuke ^{[2
]}

Koide, Shuhei ^{[5
,6
]}

Oshima, Motohiko ^{[5
,6
]}

Hishiki, Takako ^{[7
,8
]}

Hayakawa, Noriyo ^{[7
]}

Matsuura, Tomomi ^{[7
]}

Oda, Mayumi ^{[9
]}

Yanagisawa, Kiichi ^{[10
]}

Kobayashi, Hiroshi ^{[10
]}

Haraguchi, Miho ^{[10
]}

Atobe, Yoshitoshi ^{[11
]}

Funakoshi, Kengo ^{[11
]}

Iwama, Atsushi ^{[5
,6
]}

Takubo, Keiyo ^{[10
]}

Okamoto, Shinichiro ^{[1
]}

Tamura, Tomohiko ^{[3
,4
]}

Nakajima, Hideaki ^{[2
]}

机构：

[1] Keio Univ, Dept Internal Med, Div Hematol, Sch Med, Tokyo 1608582, Japan

[2] Yokohama City Univ, Dept Stem Cell & Immune Regulat, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan

[3] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 2360004, Japan

[4] Yokohama City Univ, Dept Immunol, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan

[5] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan

[6] Univ Tokyo, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci, Div Stem Cell & Mol Med, Tokyo 1088039, Japan

[7] Keio Univ, Clin & Translat Res Ctr, Sch Med, Tokyo 1608582, Japan

[8] Keio Univ, Dept Biochem, Sch Med, Tokyo 1608582, Japan

[9] Keio Univ, Dept Syst Med, Sch Med, Tokyo 1608582, Japan

[10] Natl Ctr Global Hlth & Med, Res Inst, Dept Stem Cell Biol, Tokyo 1628655, Japan

[11] Yokohama City Univ, Dept Neuroanat, Sch Med, Yokohama, Kanagawa 2360004, Japan

来源：

CELL REPORTS | 2021年 / 34卷 / 01期

关键词：

O-GLCNAC TRANSFERASE; DAMAGED MITOCHONDRIA; METABOLIC-REGULATION; TRANSCRIPTION FACTOR; SELF-RENEWAL; GLCNACYLATION; QUIESCENCE; AUTOPHAGY; PINK1; METHYLATION;

D O I：

10.1016/j.celrep.2020.108579

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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, Ogtdeficient 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.

引用

页数：21

共 50 条

[1] PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, Cristofol
Zhou, Chun
Huang, Yong
Cui, Mei
de Vries, Rosa L. A.
Kim, Jiho
May, Jessica
Tocilescu, Maja Aleksandra
Liu, Wencheng
Ko, Han Seok
Magrane, Jordi
Moore, Darren J.
Dawson, Valina L.
Grailhe, Regis
Dawson, Ted M.
Li, Chenjian
Tieu, Kim
Przedborski, Serge
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (01) : 378 - 383
[2] Short Mitochondrial ARF Triggers Parkin/PINK1-dependent Mitophagy
Grenier, Karl
Kontogiannea, Maria
Fon, Edward A.
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (43) : 29519 - 29530
[3] Atad3a suppresses Pink1-dependent mitophagy to maintain homeostasis of hematopoietic progenitor cells
Jin, Guoxiang
Xu, Chuan
Zhang, Xian
Long, Jie
Rezaeian, Abdol Hossein
Liu, Chunfang
Furth, Mark E.
Kridel, Steven
Pasche, Boris
Bian, Xiu-Wu
Lin, Hui-Kuan
NATURE IMMUNOLOGY, 2018, 19 (01) : 29 - +
[4] Inhibition of bioenergetics provides novel insights into recruitment of PINK1-dependent neuronal mitophagy
Shin, Yea Seul
Ryall, James G.
Britto, Joanne M.
Lau, Chew L.
Devenish, Rodney J.
Nagley, Phillip
Beart, Philip M.
JOURNAL OF NEUROCHEMISTRY, 2019, 149 (02) : 269 - 283
[5] Parkin- and PINK1-dependent mitophagy in neurons: will the real pathway please stand up?
Grenier, Karl
McLelland, Gian-Luca
Fon, Edward A.
FRONTIERS IN NEUROLOGY, 2013, 4
[6] Superoxide drives progression of Parkin/PINK1-dependent mitophagy following translocation of Parkin to mitochondria
Xiao, Bin
Deng, Xiao
Lim, Grace G. Y.
Xie, Shaoping
Zhou, Zhi Dong
Lim, Kah-Leong
Tan, Eng-King
CELL DEATH & DISEASE, 2017, 8 : e3097 - e3097
[7] PINK1-Dependent Mitophagy Regulates the Migration and Homing of Multiple Myeloma Cells via the MOB1B-Mediated Hippo-YAP/TAZ Pathway
Fan, Shengjun
Price, Trevor
Huang, Wei
Plue, Michelle
Warren, Jonathan
Sundaramoorthy, Pasupathi
Paul, Barry
Feinberg, Daniel
MacIver, Nancie
Chao, Nelson
Sipkins, Dorothy
Kang, Yubin
ADVANCED SCIENCE, 2020, 7 (05)
[8] Samm50 Promotes Hypertrophy by Regulating Pink1-Dependent Mitophagy Signaling in Neonatal Cardiomyocytes
Xu, Ran
Kang, Le
Wei, Siang
Yang, Chunjie
Fu, Yuanfeng
Ding, Zhiwen
Zou, Yunzeng
FRONTIERS IN CARDIOVASCULAR MEDICINE, 2021, 8
[9] Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway
Shen, James L.
Fortier, Tina M.
Wang, Ruoxi
Baehrecke, Eric H.
JOURNAL OF CELL BIOLOGY, 2021, 220 (11):
[10] PINK1-dependent mitophagy is driven by the UPS and can occur independently of LC3 conversion
Rakovic, Aleksandar
Ziegler, Jonathan
Martensson, Christoph U.
Prasuhn, Jannik
Shurkewitsch, Katharina
Koenig, Peter
Paulson, Henry L.
Klein, Christine
CELL DEATH AND DIFFERENTIATION, 2019, 26 (08): : 1428 - 1441

← 1 2 3 4 5 →