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| Status |
Public on Jan 01, 2016 |
| Title |
Irp2 mediates cigarette smoke-induced bronchitis and emphysema via regulation of cytochrome c oxidase and mitochondrial iron loading |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
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| Overall design |
1.5 X106 Beas2B cells (purchased from ATCC) with or without 10 μM DFO (16 h) (15 cm2 dishes) were washed with ice cold PBS and collected into 2 ml eppendorfs by scraping. RNA immunoprecipitation was carried out using the Magna RIP™ RNA-Binding Protein Immunoprecipitation Kit (Millipore, Billerica, MA). 4 μg of Irp2 (7H6: sc-33682, Santa Cruz, Dallas, Texas) or 4 μg of IgG rabbit control antibody (sc-2749, Santa Cruz) were added to supernatants and incubated overnight at 4°C. RNA was extracted from Magna RIP™ beads by Trizol extraction. Samples were prepared for RNA-Seq using the TruSeq RNA-Seq Lib Prep Reagent (Illumina, San Diego, CA) and performed on the Illumina HiSeq2000 platform.
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| Contributor(s) |
Cloonan S, Glass K |
| Citation(s) |
26752519 |
| Submission date |
Apr 25, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Augustine MK Choi |
| Organization name |
Weill Cornell Medical College
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| Department |
Department of Medicine
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| Street address |
525 East 68th Street, Room M-522, Box 130
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| GSM1374091 |
IRP2 immunoprecipitation from untreated cells, replicate 1 |
| GSM1374092 |
IRP2 immunoprecipitation from untreated cells, replicate 2 |
| GSM1374093 |
Immunoprecipitation with IGG antibody from untreated cells |
| GSM1374094 |
IRP2 immunoprecipitation from cells treated with DFO, replicate 1 |
| GSM1374095 |
IRP2 immunoprecipitation from cells treated with DFO, replicate 2 |
| GSM1374096 |
Immunoprecipitation with IGG antibody from cells treated with DFO |
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| Relations |
| BioProject |
PRJNA245391 |
| SRA |
SRP041444 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57073_CTRL12vsDFO12_Peaks_LowFilter.txt.gz |
623.8 Kb |
(ftp)(http) |
TXT |
| GSE57073_CTRL_Both.txt_Annotated.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE57073_DFO12vsCTRL12_Peaks_LowFilter.txt.gz |
170.6 Kb |
(ftp)(http) |
TXT |
| GSE57073_DFO_Both.txt_Annotated.txt.gz |
473.9 Kb |
(ftp)(http) |
TXT |
| GSE57073_IREB_Both.txt_Annotated.txt.gz |
430.5 Kb |
(ftp)(http) |
TXT |
| GSE57073_SC1_CONTROL_12_Peaks_LowFilter.txt.gz |
584.5 Kb |
(ftp)(http) |
TXT |
| GSE57073_SC2_DFO_12_Peaks_LowFilter.txt.gz |
306.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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