Open AccessRetinoblastoma protein promotes oxidative phosphorylation through upregulation of glycolytic genes in oncogene‐induced senescent cells
Author(s) -
Takebayashi Shinichiro,
Tanaka Hiroshi,
Hino Shinjiro,
Nakatsu Yuko,
Igata Tomoka,
Sakamoto Akihisa,
Narita Masashi,
Nakao Mitsuyoshi
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12351
Subject(s) - glycolysis , oxidative phosphorylation , biology , microbiology and biotechnology , downregulation and upregulation , senescence , flux (metallurgy) , mitochondrion , metabolic pathway , metabolome , citric acid cycle , biochemistry , metabolism , gene , chemistry , organic chemistry , metabolite
Summary 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.