Biological significance of the suppression of oxidative phosphorylation in induced pluripotent stem cells Journal Article

   

Authors:	Zhang, C.; Skamagki, M.; Liu, Z.; Ananthanarayanan, A.; Zhao, R.; Li, H.; Kim, K.
Article Title:	Biological significance of the suppression of oxidative phosphorylation in induced pluripotent stem cells
Abstract:	We discovered that induced pluripotent stem cell (iPSC) clones generated from aged tissue donors (A-iPSCs) fail to suppress oxidative phosphorylation. Compared to embryonic stem cells (ESCs) and iPSCs generated from young donors (Y-iPSCs), A-iPSCs show poor expression of the pluripotent stem cell-specific glucose transporter 3 (GLUT3) and impaired glucose uptake, making them unable to support the high glucose demands of glycolysis. Persistent oxidative phosphorylation in A-iPSCs generates higher levels of reactive oxygen species (ROS), which leads to excessive elevation of glutathione (a ROS-scavenging metabolite) and a blunted DNA damage response. These phenotypes were recapitulated in Y-iPSCs by inhibiting pyruvate dehydrogenase kinase (PDK) or supplying citrate to activate oxidative phosphorylation. In addition, oxidative phosphorylation in A-iPSC clones depletes citrate, a nuclear source of acetyl group donors for histone acetylation; this consequently alters histone acetylation status. Expression of GLUT3 in A-iPSCs recovers the metabolic defect, DNA damage response, and histone acetylation status. Zhang et al. demonstrate that GLUT3 suppresses somatic cell-specific oxidative phosphorylation in pluripotent stem cells. Low GLUT3 results in higher glutathione, blunting the DNA damage response, and citrate depletion, reducing histone acetylation. Expression of GLUT3 restores regulation. © 2017 The Authors
Keywords:	reactive oxygen species; dna damage response; oxidative phosphorylation; induced pluripotent stem cells; ros; histone acetylation; homeostatic balance
Journal Title:	Cell Reports
Volume:	21
Issue:	8
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2017-11-21
Start Page:	2058
End Page:	2065
Language:	English
DOI:	10.1016/j.celrep.2017.10.098
PROVIDER:	scopus
PUBMED:	29166598
PMCID:	PMC5841608
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85034812063&doi=10.1016%2fj.celrep.2017.10.098&partnerID=40&md5=96a1d274b6441fe38982df223128e778
Notes:	Article -- Export Date: 2 January 2018 -- Source: Scopus

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