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The Role of Endoplasmic Reticulum and Mitochondria in Maintaining Redox Status and Glycolytic Metabolism in Pluripotent Stem Cells

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Abstract

Pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells (iPSCs), can be applicable for regenerative medicine. They strangely rely on glycolysis metabolism akin to aerobic glycolysis in cancer cells. Upon differentiation, PSCs undergo a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS). The metabolic shift depends on organelles maturation, transcriptome modification, and metabolic switching. Besides, metabolism-driven chromatin regulation is necessary for cell survival, self-renewal, proliferation, senescence, and differentiation. In this respect, mitochondria may serve as key organelle to adapt environmental changes with metabolic intermediates which are necessary for maintaining PSCs identity. The endoplasmic reticulum (ER) is another organelle whose role in cellular identity remains under-explored. The purpose of our article is to highlight the recent progress on these two organelles’ role in maintaining PSCs redox status focusing on metabolism. Topics include redox status, metabolism regulation, mitochondrial dynamics, and ER stress in PSCs. They relate to the maintenance of stem cell properties and subsequent differentiation of stem cells into specific cell types.

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Abbreviations

Ac:

acetylation marks on histones

Ac-CoA:

acetyl-CoA

ACLY:

ATP-citrate lyase

ATF4:

Activation of transcription factor 4

ATF6:

Activating transcription factor 6

CHOP:

CCAAT/ enhancer-binding protein homologous-protein

CTBP:

c-terminal binding proteins

DRP1:

Dynamin-related protein 1

ERAD:

ER-associated degradation

eIF2α:

eukaryotic initiating factor 2α

FOXO1:

Forkhead box O1

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GDAP1:

Ganglioside-induced differentiation associated protein1

GRP75:

Glucose-regulated protein 75

GRP78:

Glucose regulated protein 78

GSK3β:

Glycogen synthase kinase3β

GPX:

glutathione peroxidase

HIF1-α:

Hypoxia-inducible factor1-α

HRE:

Hypoxia-responsive elements

HAT:

Histone acetyl transferase

hESCs:

human embryonic stem cells

IDO1:

Indoleamine 2,3-dioxygenase 1

IMM:

Inner membrane

IP3R:

Inositol 1,4,5-trisphosphate receptor

c-Jun N-terminal kinase:

JNK

JHDM:

JmjC-domain containing histone demethylases

MFF:

Mitochondrial fission factor

mtDNA:

Mitochondrial DNA

mTOR:

mammalian target of rapamycin

Met:

Methylation

NAD:

Nicotinamide adenine dinucleotide

Nrf2:

Nuclear factor erythroid 2 related factor 2

OMM:

Outer membrane

OPA1:

Optic atrophy protein 1

PSCs:

Pluripotent stem cells

PDK:

Pyruvate dehydrogenase kinase

PDH:

Pyruvate dehydrogenase

PINK1:

PGC1α, Peroxisome proliferator-activated receptor gamma coactivator1α

PTEN:

induced putative kinase 1

PERK:

Protein kinase-like endoplasmic reticulum kinase

REX1:

Reduced expression 1

ROS:

Reactive Oxygen Species

SOD:

Superoxide dismutase

SIRT:

Sirtuin

TET:

Ten-eleven translocation

UPR:

Unfolded protein response

VDAC:

Voltage dependent anion channel

XBP1:

X-box binding protein1

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Authors and Affiliations

  1. Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Shahnaz Babaei-Abraki

  2. Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Shahnaz Babaei-Abraki, Fereshteh Karamali & Mohammad Hossein Nasr-Esfahani

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  1. Shahnaz Babaei-Abraki
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  2. Fereshteh Karamali
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Babaei-Abraki: conceptualization, literature search, original draft writing, and editing. Karamali: contributed to the study conception, design, and editing. Nasr-Esfahani: critically reviewed the manuscript, supervision it, and approved the final version to be published. All authors read and approved the final manuscript.

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Correspondence to Mohammad Hossein Nasr-Esfahani.

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Babaei-Abraki, S., Karamali, F. & Nasr-Esfahani, M.H. The Role of Endoplasmic Reticulum and Mitochondria in Maintaining Redox Status and Glycolytic Metabolism in Pluripotent Stem Cells. Stem Cell Rev and Rep 18, 1789–1808 (2022). https://doi.org/10.1007/s12015-022-10338-8

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