Role of mitochondrial fission-related genes in mitochondrial morphology and energy metabolism in mouse embryonic stem cells.

Redox Biology
Bong Jong SeoJeong Tae Do

Abstract

Mitochondria, the major organelles that produce energy for cell survival and function, dynamically change their morphology via fusion and fission, a process called mitochondrial dynamics. The details of the underlying mechanism of mitochondrial dynamics have not yet been elucidated. Here, we aimed to investigate the function of mitochondrial fission genes in embryonic stem cells (ESCs). To this end, we generated homozygous knockout ESC lines, namely, Fis1-/-, Mff-/-, and Dnm1l-/- ESCs, using the CRISPR-Cas9 system. Interestingly, the Fis1-/-, Mff-/-, and Dnm1l-/- ESCs showed normal morphology, self-renewal, and the ability to differentiate into all three germ layers in vitro. However, transmission electron microscopy showed a significant increase in the cytoplasm to nucleus ratio and mitochondrial elongation in Dnm1l-/- ESCs, which was due to incomplete fission. To assess the change in metabolic energy, we analyzed oxidative phosphorylation (OXPHOS), glycolysis, and the intracellular ATP concentration. The ESC knockout lines showed an increase in OXPHOS, decrease in glycolysis, and an increase in intracellular ATP concentration, which was related to mitochondrial elongation. In particular, the Dnm1l knockout most significantly ...Continue Reading

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Citations

Jan 12, 2021·Frontiers in Cell and Developmental Biology·Vishnu K KumarPriscila Y Sato
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Marcia GarcezCatarina C F Homem
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Qing-Yuan GaoYang-Xin Chen

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Datasets Mentioned

BETA
MAB1637

Methods Mentioned

BETA
gene knockout
transfection
PCR
electron microscopy
gene knockouts
SMA
transmission electron microscopy
RNA-seq
gene

Software Mentioned

ImageJ
OCR
gplots
Relative Quantification
STAR
Image J
StringTie
R
DAVID
ECAR

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