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Oncotarget. 2016 May 10;7(19):28286-300. doi: 10.18632/oncotarget.8536.

Apoptotic transition of senescent cells accompanied with mitochondrial hyper-function.

Author information

1
Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
2
Division of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
3
Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, China.

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.

KEYWORDS:

ROS; apoptosis; metabolism; mitochondria; senescence

PMID:
27056883
PMCID:
PMC5053727
DOI:
10.18632/oncotarget.8536
[Indexed for MEDLINE]
Free PMC Article

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