Mitochondrial dysfunction is induced by the overexpression of UCP4 in 3T3-L1 adipocytes
| Autor: | Chun-Lin Gao, Xiao-Hui Chen, Chen-Bo Ji, Yu-zhu Peng, Chun Zhu, Ya-Ping Zhao, Chun-Mei Zhang, Zheng-Kun Xia, Xirong Guo, Jingai Zhu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
DNA Copy Number Variations MFN2 Mitochondrion Biology DNA Mitochondrial Mice chemistry.chemical_compound Adenosine Triphosphate 3T3-L1 Cells Adipocyte Internal medicine Adipocytes Genetics medicine Animals Uncoupling protein MFN1 Membrane Potential Mitochondrial Membrane Transport Proteins General Medicine TFAM Mitochondria Up-Regulation Cell biology Glucose Endocrinology Mitochondrial biogenesis chemistry mitochondrial fusion Calcium Mitochondrial Uncoupling Proteins Reactive Oxygen Species |
| Zdroj: | International Journal of Molecular Medicine. 25 |
| ISSN: | 1107-3756 |
| DOI: | 10.3892/ijmm_00000315 |
| Popis: | Uncoupling proteins (UCPs) belong to a superfamily of mitochondrial transporters that uncouple ATP synthesis from electron transport. We have previously shown that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats. Overexpression of UCP4 promotes proliferation and inhibits apoptosis and differentiation of preadipocytes. In this work, we further characterized the effect of UCP4 on mitochondrial function in mature 3T3-L1 adipocytes. Transmission electron microscopy (TEM) showed that adipocytes overexpressing UCP4 displayed condensed mitochondria with twisted, condensed, and unclear cristae. Moreover, the loss of the mitochondrial membrane potential and intramitochondrial calcium was found. The adipocytes overexpressing UCP4 also showed decreased mitochondrial copy number (mtDNA) and lower mRNA expression of key factors in mitochondrial biogenesis, including PGC-1alpha and mtTFA. NRF-1 and ERRbeta levels were down-regulated, while NRF-2 levels were upregulated. In addition, UCP4 overexpression impaired mitochondrial fusion and fission, as indicated by decreased mitofusin mfn1, mfn2, and mitofission DRP1. When it came to total adipocytes, the UCP4 overexpressing adipocytes showed higher production reactive oxygen species and diminished levels of intracellular ATP. Furthermore, overexpression of UCP4 brought about impaired insulin sensitivity in adipocytes. UCP4 plays an important role in mitochondrial function and adipocyte insulin resistance. Its function deserves further attention. |
| Databáze: | OpenAIRE |
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