Abstract |
Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors essential for cytokine signaling. Our previous study showed that interleukin-3 (IL-3) induced STAT5 translocation to mitochondria and binding to mitochondrial DNA ( mtDNA) in vitro. In this report, we further demonstrated in vivo binding of endogenous STAT5a to mtDNA transcriptional control region and reduced gene expression from all three mtDNA promoters after IL-3 stimulation. To specifically define the function of mitochondrial STAT5a, we generated mitochondrial-targeting wild-type and mutant STAT5a proteins. Compared with non-targeting STAT5a, mitochondrial-targeting wild-type STAT5a significantly reduced mitochondrial gene expression in transfected HEK293 cells. The level of attenuation was amplified in cells expressing constitutively active STAT5a, but abrogated in cells expressing DNA-binding-defective STAT5a. STAT5a-mediated repression of mtDNA expression also positively correlated with STAT5a binding to the E2 subunit of pyruvate dehydrogenase complex (PDC-E2), both a gate-keeping metabolic enzyme and a component of mtDNA nucleoid in mitochondrial matrix. Metabolic shift away from mitochondrial respiration is known in many cytokine-stimulated cells and cancer cells. STAT5a-mediated repression of mitochondrial gene expression and its interaction with PDC-E2 may provide important insights into its underlying mechanisms.
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Authors | Fu-Yu Chueh, Ying-Ling Chang, Shin-Yu Wu, Chao-Lan Yu |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 527
Issue 4
Pg. 974-978
(07 05 2020)
ISSN: 1090-2104 [Electronic] United States |
PMID | 32446558
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- DNA, Mitochondrial
- STAT5 Transcription Factor
- Stat5a protein, mouse
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Topics |
- Animals
- Cell Line
- DNA, Mitochondrial
(genetics, metabolism)
- Down-Regulation
- Gene Expression
- Genes, Mitochondrial
- HEK293 Cells
- Humans
- Mice
- Mitochondria
(genetics, metabolism)
- Mutation
- STAT5 Transcription Factor
(genetics, metabolism)
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