論文

査読有り
2015年8月

Retinoblastoma protein promotes oxidative phosphorylation through upregulation of glycolytic genes in oncogene-induced senescent cells

AGING CELL
  • Shin-ichiro Takebayashi
  • ,
  • Hiroshi Tanaka
  • ,
  • Shinjiro Hino
  • ,
  • Yuko Nakatsu
  • ,
  • Tomoka Igata
  • ,
  • Akihisa Sakamoto
  • ,
  • Masashi Narita
  • ,
  • Mitsuyoshi Nakao

14
4
開始ページ
689
終了ページ
697
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/acel.12351
出版者・発行元
WILEY-BLACKWELL

Metabolism is closely linked with cellular state and biological processes, but the mechanisms controlling metabolic properties in different contexts remain unclear. Cellular senescence is an irreversible growth arrest induced by various stresses, which exhibits active secretory and metabolic phenotypes. Here, we show that retinoblastoma protein (RB) plays a critical role in promoting the metabolic flow by activating both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) in cells that have undergone oncogene-induced senescence (OIS). A combination of real-time metabolic monitoring, and metabolome and gene expression analyses showed that OIS-induced fibroblasts developed an accelerated metabolic flow. The loss of RB downregulated a series of glycolytic genes and simultaneously reduced metabolites produced from the glycolytic pathway, indicating that RB upregulates glycolytic genes in OIS cells. Importantly, both mitochondrial OXPHOS and glycolytic activities were abolished in RB-depleted or downstream glycolytic enzyme-depleted OIS cells, suggesting that RB-mediated glycolytic activation induces a metabolic flux into the OXPHOS pathway. Collectively, our findings reveal that RB essentially functions in metabolic remodeling and the maintenance of the active energy production in OIS cells.

Web of Science ® 被引用回数 : 30

リンク情報
DOI
https://doi.org/10.1111/acel.12351
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000357941900018&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/acel.12351
  • ISSN : 1474-9718
  • eISSN : 1474-9726
  • Web of Science ID : WOS:000357941900018

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