Abstract |
Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.
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Authors | Jun Zhang, Yu Peng, Haosen Song, Siqi Liu, Chuanwei Li, Yi Zhang, Xiaowei Shi, Huifang Guo, Yingping Xu |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 133
Pg. 112012
(May 30 2024)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 38657501
(Publication Type: Journal Article)
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Copyright | Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved. |
Chemical References |
- DNA-Binding Proteins
- Transcription Factors
- Tfam protein, mouse
- Mitochondrial Proteins
- Adenosine Triphosphate
- High Mobility Group Proteins
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Topics |
- Oxidative Phosphorylation
- Animals
- Macrophages, Alveolar
(metabolism)
- Mitochondria
(metabolism)
- Mice
- Lung
(metabolism)
- Adaptation, Physiological
- DNA-Binding Proteins
(metabolism, genetics)
- Transcription Factors
(metabolism, genetics)
- Endoplasmic Reticulum Stress
- Mice, Knockout
- Apoptosis
- Mice, Inbred C57BL
- Mitochondrial Proteins
(metabolism, genetics)
- Female
- Glycolysis
- Adenosine Triphosphate
(metabolism)
- High Mobility Group Proteins
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