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Mitochondrial permeability transition regulator, cyclophilin D, is transcriptionally activated by C/EBP during adipogenesis

The Journal of biological chemistry, 2023-12, Vol.299 (12), p.105458-105458, Article 105458 [Peer Reviewed Journal]

2023 The Authors ;Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. ;2023 The Authors 2023 ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1016/j.jbc.2023.105458 ;PMID: 37949231

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  • Title:
    Mitochondrial permeability transition regulator, cyclophilin D, is transcriptionally activated by C/EBP during adipogenesis
  • Author: Yu, Chen ; Sautchuk, Rubens ; Martinez, John ; Eliseev, Roman A.
  • Subjects: Adipogenesis ; Aging ; C/EBP ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; cyclophilin D ; Glycolysis ; Inflammation - metabolism ; mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - metabolism ; Mitochondria - metabolism ; mitochondrial permeability transition ; Mitochondrial Permeability Transition Pore - metabolism ; Peptidyl-Prolyl Isomerase F - genetics ; Peptidyl-Prolyl Isomerase F - metabolism ; Transcription Factor RelA
  • Is Part Of: The Journal of biological chemistry, 2023-12, Vol.299 (12), p.105458-105458, Article 105458
  • Description: Age-related bone loss is associated with decreased bone formation, increased bone resorption, and accumulation of bone marrow fat. During aging, differentiation potential of bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) is shifted toward an adipogenic lineage and away from an osteogenic lineage. In aged bone tissue, we previously observed pathological opening of the mitochondrial permeability transition pore (MPTP) which leads to mitochondrial dysfunction, oxidative phosphorylation uncoupling, and cell death. Cyclophilin D (CypD) is a mitochondrial protein that facilitates opening of the MPTP. We found earlier that CypD is downregulated during osteogenesis of BMSCs leading to lower MPTP activity and, thus, protecting mitochondria from dysfunction. However, during adipogenesis, a fate alternative to osteogenesis, the regulation of mitochondrial function and CypD expression is still unclear. In this study, we observed that BMSCs have increased CypD expression and MPTP activity, activated glycolysis, and fragmented mitochondrial network during adipogenesis. Adipogenic C/EBPα acts as a transcriptional activator of expression of the CypD gene, Ppif, during this process. Inflammation-associated transcription factor NF-κB shows a synergistic effect with C/EBPα inducing Ppif expression. Overall, we demonstrated changes in mitochondrial morphology and function during adipogenesis. We also identified C/EBPα as a transcriptional activator of CypD. The synergistic activation of CypD by C/EBPα and the NF-κB p65 subunit during this process suggests a potential link between adipogenic signaling, inflammation, and MPTP gain-of-function, thus altering BMSC fate during aging.
  • Publisher: United States: Elsevier Inc
  • Language: English
  • Identifier: ISSN: 0021-9258
    EISSN: 1083-351X
    DOI: 10.1016/j.jbc.2023.105458
    PMID: 37949231
  • Source: MEDLINE
    PubMed Central
    Directory of Open Access Journals
    Alma/SFX Local Collection
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