Cyclophilin-D: a resident regulator of mitochondrial gene expression
| Autor: | Bala Chandran, Raúl J. Gazmuri, Jeejabai Radhakrishnan, Stanley Bazarek |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Mitochondrial DNA
Green Fluorescent Proteins Down-Regulation urologic and male genital diseases Transfection Biochemistry Oxidative Phosphorylation Mitochondrial Proteins Cyclophilins Transcription (biology) Genetics Gene silencing Cytochrome c oxidase Humans heterocyclic compounds Gene Silencing Promoter Regions Genetic Molecular Biology Cyclophilin Regulator gene Membrane Potential Mitochondrial biology Chemistry organic chemicals NADH dehydrogenase NADH Dehydrogenase Methyltransferases respiratory system Mitochondrial Proton-Translocating ATPases Molecular biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Genes Mitochondrial HEK293 Cells Gene Expression Regulation Mitochondrial matrix biology.protein Cyclooxygenase 1 Biotechnology Transcription Factors |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 29(7) |
| ISSN: | 1530-6860 |
| Popis: | Cyclophilin-D (Cyp-D) is a mitochondrial matrix peptidyl-prolyl isomerase. Because cyclophilins can regulate nuclear gene expression, we examined whether Cyp-D could regulate mitochondrial gene expression. We demonstrated in HEK 293T cells that transfected Cyp-D interacts with mitochondrial transcription factors B1 and B2 (TFB2M) but not with mitochondrial transcription factor A. We also demonstrated that Cyp-D interacts in vivo with TFB2M. Genetic silencing of Cyp-D and pharmacologic inhibition of Cyp-D markedly reduced mitochondrial transcription to 18 ± 5% (P0.05) and 24 ± 3% (P0.05) of respective controls. The level of interaction between Cyp-D and TFB2M correlated with the level of nascent mitochondrial RNA intensity (r = 0.896; P = 0.0156). Cyp-D silencing down-regulated mitochondrial transcripts initiated from the heavy strand promoter 2 [i.e., NADH dehydrogenase 1 (ND1) by 11-fold, P0.005; cytochrome oxidase 1 (COX1) by 4-fold, P0.001; and ATP synthase subunit 6 (ATP6) by 6.5-fold, P0.005); but not NADH dehydrogenase 6 (ND6)], which is initiated from the light strand promoter. Cyp-D silencing reduced mitochondrial membrane potential and cellular oxygen consumption (from 59 ± 5 to 34 ± 1 µmol oxygen/min/10(6) cells, P0.001); the latter without a statistically significant reversal after uncoupling electron transport from ATP synthesis, consistent with down-regulation of electron transport complexes. Accordingly, these studies provide novel evidence that Cyp-D could play a key role in regulating mitochondrial gene expression. |
| Databáze: | OpenAIRE |
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