Document Detail


UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells.
MedLine Citation:
PMID:  22085932     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O(2) at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F(1)F(0) ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential.
Authors:
Jin Zhang; Ivan Khvorostov; Jason S Hong; Yavuz Oktay; Laurent Vergnes; Esther Nuebel; Paulin N Wahjudi; Kiyoko Setoguchi; Geng Wang; Anna Do; Hea-Jin Jung; J Michael McCaffery; Irwin J Kurland; Karen Reue; Wai-Nang P Lee; Carla M Koehler; Michael A Teitell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-15
Journal Detail:
Title:  The EMBO journal     Volume:  30     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-01-30     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4860-73     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate
Cell Differentiation*
Cell Line
Energy Metabolism*
Glycolysis
Humans
Hydrolysis
Ion Channels / genetics,  metabolism*
Mitochondria / metabolism*
Mitochondrial Proteins / genetics,  metabolism*
Oxygen Consumption
Pluripotent Stem Cells / cytology*,  metabolism*,  ultrastructure
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
CA156674/CA/NCI NIH HHS; CA90571/CA/NCI NIH HHS; DK58132/DK/NIDDK NIH HHS; GM061721/GM/NIGMS NIH HHS; GM073981/GM/NIGMS NIH HHS; M01-RR00425/RR/NCRR NIH HHS; P01 HL028481/HL/NHLBI NIH HHS; P01GM081621/GM/NIGMS NIH HHS; PNEY018228//PHS HHS; R01 CA090571/CA/NCI NIH HHS; R01 CA156674/CA/NCI NIH HHS; R01 GM061721/GM/NIGMS NIH HHS; R01 GM073981/GM/NIGMS NIH HHS; S10RR026744/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 0/mitochondrial uncoupling protein 2; 8L70Q75FXE/Adenosine Triphosphate
Comments/Corrections
Comment In:
EMBO J. 2011 Dec 14;30(24):4851-2   [PMID:  22166995 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1.
Next Document:  FGF signalling inhibits neural induction in human embryonic stem cells.