title: Apoptotic transition of senescent cells accompanied with mitochondrial hyper-function.
abstract: Defined as stable cell-cycle arrest, cellular senescence plays an important role in diverse biological processes including tumorigenesis, organismal aging, and embryonic development. Although increasing evidence has documented the metabolic changes in senescent cells, mitochondrial function and its potential contribution to the fate of senescent cells remain largely unknown. Here, using two in vitro models of cellular senescence induced by doxorubicin treatment and prolonged passaging of neonatal human foreskin fibroblasts, we report that senescent cells exhibited high ROS level and augmented glucose metabolic rate concomitant with both morphological and quantitative changes of mitochondria. Furthermore, mitochondrial membrane potential depolarized at late stage of senescent cells which eventually led to apoptosis. Our study reveals that mitochondrial hyper-function contributes to the implementation of cellular senescence and we propose a model in which the mitochondrion acts as the key player in promoting fate-determination in senescent cells.
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Danli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Weihao
authors.initials: W
authors.lastname: Sui
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Division of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
authors.forename: Feiqiu
authors.initials: F
authors.lastname: Wen
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ouyang
authors.affiliation: Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.|Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Ji
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology
chemical_list: D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin
keywords: ROS; apoptosis; metabolism; mitochondria; senescence