Intact mitochondrial function in the setting of telomere-induced senescence.
Intact mitochondrial function in the setting of telomere-induced senescence.
复制标题
完整的线粒体功能在端粒诱导衰老的设置。
作者：
线粒体在所有细胞内的代谢支持和信号传导中发挥重要作用。线粒体的先天性和后天性缺陷是导致几种病理的原因，包括过早进入细胞衰老。相反，我们研究了功能失调的端粒驱动的细胞衰老对线粒体生物发生和功能的影响。我们分别通过删除成纤维细胞和肝细胞中的端粒结合蛋白TRF2来驱动体外和体内衰老。TRF2的缺失导致强有力的DNA损伤反应、转录的全局变化和细胞衰老的诱导。在体外，衰老细胞具有由细胞和线粒体体积增加驱动的线粒体呼吸能力的显著增加。端粒功能障碍的肝细胞在体内维持其线粒体呼吸能力，无论是在完整细胞还是纯化的线粒体中测量。衰老的诱导导致成纤维细胞和肝细胞中重叠和不同基因的上调，但线粒体相关的转录物被保留。我们的研究结果支持线粒体功能和活性在端粒功能障碍诱导的衰老中得以保留，这可能有助于细胞功能的持续。细胞衰老引起细胞内的一系列变化，包括细胞形态、转录和分泌行为的改变。Sullivan等人研究了端粒功能障碍对体外成纤维细胞线粒体和体内肝细胞的影响。他们发现，线粒体功能在体外和体内细胞衰老期间都得到了显着的保护。
Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere‐driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere‐binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction‐induced senescence, which may facilitate continued cellular functions. Cellular senescence brings about a constellation of changes within cells including altered cellular morphology, transcription, and secretory behavior. Sullivan et al. examined the consequences of telomere dysfunction on mitochondria in fibroblasts in vitro and on hepatocytes in vivo. They found that mitochondrial function was remarkably preserved during cellular senescence in vitro as well as in vivo.
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影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
7.7
作者：
Chan M;Yuan H;Soifer I;Maile TM;Wang RY;Ireland A;O'Brien JJ;Goudeau J;Chan LJG;Vijay T;Freund A;Kenyon C;Bennett BD;McAllister FE;Kelley DR;Roy M;Cohen RL;Levinson AD;Botstein D;Hendrickson DG
通讯作者：
Hendrickson DG
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J