ID 112955
Title Alternative
A Critical Role of Mitochondrial ATP Supply in Neutrophil Differentiation
Author
Tanimura, Ayako Prefectural University of Kumamoto|Tokushima University KAKEN Search Researchers
Hagita, Hiroko Tokushima University
Fujisawa, Koichi Yamaguchi University
Keywords
ATP
ER stress
HL-60
Mitochondria
Myelocytic differentiation
Unfolded protein response
Content Type
Journal Article
Description
Background/Aims: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in hematopoietic differentiation. However, the mechanistic linkage between ER stress/UPR and hematopoietic differentiation remains unclear. Methods: We used bipotent HL-60 cells as an in vitro hematopoietic differentiation system to investigate the role of ER stress and UPR activity in neutrophil and macrophage differentiation. Results: The in vitro differentiation analysis revealed that ER stress decreased during both neutrophil and macrophage differentiations, and the activities of PERK and ATF6 were decreased and that of IRE1α was increased during neutrophil differentiation in a stage-specific manner. By contrast, the activities of ATF6 and ATF4 decreased during macrophage differentiation. When the cells were treated with oligomycin, the expression of CD11b, a myelocytic differentiation marker, and morphological differentiation were suppressed, and XBP-1 activation was inhibited during neutrophil differentiation, whereas CD11b expression was maintained, and morphological differentiation was not obviously affected during macrophage differentiation. Conclusion: In this study, we demonstrated that neutrophil differentiation is regulated by ER stress/UPR that is supported by mitochondrial ATP supply, in which IRE1α-XBP1 activation is essential. Our findings provide the evidence that mitochondrial energy metabolism may play a critical role in neutrophil differentiation.
Journal Title
Cellular Physiology and Biochemistry
ISSN
10158987
14219778
NCID
AA10801409
AA12780988
Publisher
S. Karger AG, Basel
Volume
47
Issue
5
Start Page
1936
End Page
1950
Published Date
2018-07-03
Rights
© 2018 The Author(s). This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
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language
eng
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departments
Oral Sciences