ID | 112955 |
Title Alternative | A Critical Role of Mitochondrial ATP Supply in Neutrophil Differentiation
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Author |
Miyoshi, Keiko
Tokushima University
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Horiguchi, Taigo
Tokushima University
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Hagita, Hiroko
Tokushima University
Fujisawa, Koichi
Yamaguchi University
Noma, Takafumi
Tokushima University
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Keywords | ATP
ER stress
HL-60
Mitochondria
Myelocytic differentiation
Unfolded protein response
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Content Type |
Journal Article
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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.
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Journal Title |
Cellular Physiology and Biochemistry
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ISSN | 10158987
14219778
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NCID | AA10801409
AA12780988
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Publisher | S. Karger AG, Basel
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Volume | 47
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Issue | 5
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Start Page | 1936
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End Page | 1950
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Published Date | 2018-07-03
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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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Publisher
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departments |
Oral Sciences
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