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Defects in mtDNA replication challenge nuclear genome stability through nucleotide depletion and provide a unifying mechanism for mouse progerias.

Abstract:
Mitochondrial DNA (mtDNA) mutagenesis and nuclear DNA repair defects are considered cellular mechanisms of ageing. mtDNA mutator mice with increased mtDNA mutagenesis show signs of premature ageing. However, why patients with mitochondrial diseases, or mice with other forms of mitochondrial dysfunction, do not age prematurely remains unknown. Here, we show that cells from mutator mice display challenged nuclear genome maintenance similar to that observed in progeric cells with defects in nuclear DNA repair. Cells from mutator mice show slow nuclear DNA replication fork progression, cell cycle stalling and chronic DNA replication stress, leading to double-strand DNA breaks in proliferating progenitor or stem cells. The underlying mechanism involves increased mtDNA replication frequency, sequestering of nucleotides to mitochondria, depletion of total cellular nucleotide pools, decreased deoxynucleoside 5 -triphosphate (dNTP) availability for nuclear genome replication and compromised nuclear genome maintenance. Our data indicate that defects in mtDNA replication can challenge nuclear genome stability. We suggest that defects in nuclear genome maintenance, particularly in the stem cell compartment, represent a unified mechanism for mouse progerias. Therefore, through their destabilizing effects on the nuclear genome, mtDNA mutations are indirect contributors to organismal ageing, suggesting that the direct role of mtDNA mutations in driving ageing-like symptoms might need to be revisited.
Author Listing: Riikka H. Hämäläinen;Juan Cruz Landoni;Kati Ahlqvist;Steffi Goffart;Sanna Ryytty;M. Obaidur Rahman;Virginia Brilhante;Katherine Icay;Sampsa Hautaniemi;Liya Wang;Marikki Laiho;Anu Suomalainen
Volume: 1 10
Pages: \n 958-965\n
DOI: 10.1038/s42255-019-0120-1
Language: English
Journal: Nature metabolism

Nature Metabolism

NAT METAB

影响因子:20.8
是否综述期刊:是
是否OA:否
是否预警:不在预警名单内
发行时间:-
ISSN:2522-5812
发刊频率:12 issues per year
收录数据库:SCIE/Scopus收录
出版国家/地区:ENGLAND
出版社:NATURE RESEARCH

期刊介绍

Nature Metabolism will publish work from across all fields of metabolism research that significantly advances our understanding of metabolic and homeostatic processes in a cellular or broader physiological context, from fundamental cell biology to basic biomedical and translational research. At its core, the research published in Nature Metabolism will shed light on how cellular metabolism informs cellular function, on the physiology and homeostasis of organs and tissues, on the regulation of organismal energy homeostasis, and on the molecular pathophysiology of metabolic diseases, such as diabetes and obesity, or the treatment thereof.

Nature Metabolism将发表所有代谢研究领域的成果,这些成果将显著推进我们对细胞或更广泛的生理学背景下的代谢和稳态过程的理解,从基础细胞生物学到基础生物医学和转化研究。发表在《自然代谢》杂志上的这项研究的核心内容将阐明细胞代谢如何影响细胞功能、器官和组织的生理学和稳态、有机体能量稳态的调节以及代谢疾病(如糖尿病和肥胖症)的分子病理生理学或其治疗。

年发文量 194
国人发稿量 52
国人发文占比 26.71%
自引率 1.9%
平均录取率 -
平均审稿周期 -
版面费 -
偏重研究方向 ENDOCRINOLOGY & METABOLISM-
期刊官网 https://www.nature.com/natmetab/?utm_medium=display&utm_source=letpub&utm_content=text_link&utm_term=null&utm_campaign=MLSR_42255_AWA1_CN_CNPL_letpb_mp
投稿链接 https://mts-natmetab.nature.com/

质量指标占比

研究类文章占比 OA被引用占比 撤稿占比 出版后修正文章占比
90.72% 30.16% - -

相关指数

影响因子
影响因子
年发文量
自引率
Cite Score

预警情况

时间 预警情况
2025年03月发布的2025版 不在预警名单中
2024年02月发布的2024版 不在预警名单中
2023年01月发布的2023版 不在预警名单中
2021年12月发布的2021版 不在预警名单中
2020年12月发布的2020版 不在预警名单中

JCR分区 WOS分区等级:Q1区

版本 按学科 分区
WOS期刊SCI分区
(2021-2022年最新版)
ENDOCRINOLOGY & METABOLISM Q1

中科院分区

版本 大类学科 小类学科 Top期刊 综述期刊
医学
1区
ENDOCRINOLOGY & METABOLISM
内分泌学与代谢
1区
2021年12月
基础版
医学
1区
ENDOCRINOLOGY & METABOLISM
内分泌学与代谢
1区
2021年12月
升级版
医学
1区
ENDOCRINOLOGY & METABOLISM
内分泌学与代谢
1区
2022年12月
最新升级版
医学
1区
ENDOCRINOLOGY & METABOLISM
内分泌学与代谢
1区