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Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells
Ren,Zhili1,2; Zhong,Hui1,2; Song,Chengcheng1,2; Deng,Chunhao1,2; Hsieh,Hsun Ting3; Liu,Weiwei1,3; Chen,Guokai1,2
2020-12-08
Source PublicationStem Cell Reports
ISSN2213-6711
Volume15Issue:6Pages:1362-1376
Abstract

Insulin is an essential growth factor for the survival and self-renewal of human embryonic stem cells (hESCs). Although it is best known as the principal hormone promoting glycolysis in somatic cells, insulin's roles in hESC energy metabolism remain unclear. In this report, we demonstrate that insulin is essential to sustain hESC mitochondrial respiration that is rapidly decreased upon insulin removal. Insulin-dependent mitochondrial respiration is stem cell specific, and mainly relies on pyruvate and glutamine, while glucose suppresses excessive oxidative phosphorylation. Pharmacologic and genetic manipulations reveal that continuous insulin signal sustains mitochondrial respiration through PI3K/AKT activation and downstream GSK3 inhibition. We further show that insulin acts through GSK3 inhibition to suppress caspase activation and rescue cell survival. This study uncovers a critical role of the AKT/GSK3 pathway in the regulation of mitochondrial respiration and cell survival, highlighting insulin as an essential factor for accurate assessment of mitochondrial respiration in hESCs.

KeywordAkt Caspase Cell Survival Gsk3 Human Embryonic Stem Cells Insulin Mitochondrial Respiration
DOI10.1016/j.stemcr.2020.10.008
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell & Tissue Engineering ; Cell Biology
WOS IDWOS:000599616800006
PublisherCELL PRESS
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorChen,Guokai
Affiliation1.Centre of Reproduction,Development and Aging,Faculty of Health Sciences,University of Macau,Macau SAR,Taipa,China
2.Institute of Translational Medicine,Faculty of Health Sciences,University of Macau,Macau SAR,China
3.Bioimaging and Stem Cell Core Facility,Faculty of Health Sciences,University of Macau,Macau SAR,China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Ren,Zhili,Zhong,Hui,Song,Chengcheng,et al. Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells[J]. Stem Cell Reports,2020,15(6):1362-1376.
APA Ren,Zhili.,Zhong,Hui.,Song,Chengcheng.,Deng,Chunhao.,Hsieh,Hsun Ting.,...&Chen,Guokai.(2020).Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells.Stem Cell Reports,15(6),1362-1376.
MLA Ren,Zhili,et al."Insulin Promotes Mitochondrial Respiration and Survival through PI3K/AKT/GSK3 Pathway in Human Embryonic Stem Cells".Stem Cell Reports 15.6(2020):1362-1376.
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