Summary of Study ST003248
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002016. The data can be accessed directly via it's Project DOI: 10.21228/M81C00 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003248 |
| Study Title | Effects of acute mitoregulin loss on cardiac mitochondrial lipids in mice |
| Study Summary | Cardiac mitochondrial lipidome analysis in 7-week-old male aMHC-Cas9 transgenic mice, harvested at 4 weeks post-injection with either AAV:guMtln (sgRNAs to delete Mtln) or AAV:GFP control. |
| Institute | University of Iowa |
| Last Name | Boudreau |
| First Name | Ryan |
| Address | 4334 PBDB, 169 Newton Rd, Iowa City, IA 52242 |
| ryan-boudreau@uiowa.edu | |
| Phone | 3193535573 |
| Submit Date | 2024-06-05 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-12-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002016 |
| Project DOI: | doi: 10.21228/M81C00 |
| Project Title: | Effects of mitoregulin loss on cardiac and mitochondrial lipids in mice |
| Project Summary: | We and others discovered a highly-conserved mitochondrial transmembrane microprotein, named Mitoregulin (Mtln), that supports lipid metabolism. We reported that Mtln strongly binds cardiolipin (CL), increases mitochondrial respiration and Ca2+ retention capacities, and reduces reactive oxygen species (ROS). Here we extend our observation of Mtln-CL binding and examine Mtln influence on cristae structure and mitochondrial membrane integrity during stress. We demonstrate that mitochondria from constitutive- and inducible Mtln-knockout (KO) mice are susceptible to membrane freeze-damage and that this can be rescued by acute Mtln re-expression. In mitochondrial-simulated lipid monolayers, we show that synthetic Mtln decreases lipid packing and monolayer elasticity. Lipidomics revealed that Mtln-KO heart tissues show broad decreases in 22:6-containing lipids and increased cardiolipin damage/remodeling. Lastly, we demonstrate that Mtln-KO mice suffer worse myocardial ischemia-reperfusion injury, hinting at a translationally-relevant role for Mtln in cardioprotection. Our work supports a model in which Mtln binds cardiolipin and stabilizes mitochondrial membranes to broadly influence diverse mitochondrial functions, including lipid metabolism, while also protecting against stress. |
| Institute: | University of Iowa |
| Last Name: | Boudreau |
| First Name: | Ryan |
| Address: | 4334 PBDB, 169 Newton Rd, Iowa City, IA 52242 |
| Email: | ryan-boudreau@uiowa.edu |
| Phone: | 3193535573 |
Subject:
| Subject ID: | SU003367 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA353473 | 3058-1 | acute ko |
| SA353474 | 3058-2 | acute ko |
| SA353475 | 3097-3 | acute ko |
| SA353476 | 3097-4 | acute ko |
| SA353477 | 3109-1 | acute ko |
| SA353478 | 3109-3 | acute ko |
| SA353479 | 3058-3 | cntrl |
| SA353480 | 3058-4 | cntrl |
| SA353481 | 3097-1 | cntrl |
| SA353482 | 3109-2 | cntrl |
| SA353483 | 3116-1 | cntrl |
| SA353484 | 3116-2 | cntrl |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO003360 |
| Collection Summary: | Mitochondria were isolated from hearts of 6 AAV9:GFP injected and 6 AAV9:guMtln injected aMHC-Cas9 transgenic mice at approximately 7 weeks of age (4 weeks post AAV injection) and mitochondrial pellets stored at -80. Protein content of mitochondrial pellets was determined by BCA assay of distinct, paired pellets (collected from the same homogenate), after detergent solubilization. |
| Sample Type: | Heart |
Treatment:
| Treatment ID: | TR003376 |
| Treatment Summary: | No treatment. |
Sample Preparation:
| Sampleprep ID: | SP003374 |
| Sampleprep Summary: | Mitochondria were isolated from hearts of 6 AAV9:GFP injected and 6 AAV9:guMtln injected aMHC-Cas9 transgenic mice at approximately 7 weeks of age (4 weeks post AAV injection) and mitochondrial pellets stored at -80. Protein content of mitochondrial pellets was determined by BCA assay of distinct, paired pellets (collected from the same homogenate), after detergent solubilization. |
Chromatography:
| Chromatography ID: | CH004024 |
| Chromatography Summary: | Positive Mode RP LCMS |
| Instrument Name: | Agilent 1290 Infinity |
| Column Name: | Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 65 |
| Flow Gradient: | Started at 15% mobile phase B then increased to 30% B over 2.4 min. It sequentially increased to 48% B from 2.4 – 3.0 min, 82% B from 3 – 13.2 min, and 99% B from 13.2 – 13.8 min where it’s held until 16.7 min and returned to the initial conditions and equilibrated for 5 min. |
| Flow Rate: | 0.4 mL min |
| Solvent A: | 40% water/60% acetonitrile; 0.1% formic acid; 10 mM ammonium formate |
| Solvent B: | 90% isopropanol/9% acetonitrile/1% water; 0.1% formic acid; 10 mM ammonium formate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004025 |
| Chromatography Summary: | Negative Mode RP LCMS |
| Instrument Name: | Agilent 1290 Infinity |
| Column Name: | Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 65 |
| Flow Gradient: | Started at 15% mobile phase B then increased to 30% B over 2.4 min. It sequentially increased to 48% B from 2.4 – 3.0 min, 82% B from 3 – 13.2 min, and 99% B from 13.2 – 13.8 min where it’s held until 16.7 min and returned to the initial conditions and equilibrated for 5 min. |
| Flow Rate: | 0.4 mL min |
| Solvent A: | 40% water/60% acetonitrile; 10 mM ammonium formate |
| Solvent B: | 90% isopropanol/9% acetonitrile/1% water; 10 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN005320 |
| Analysis Type: | MS |
| Chromatography ID: | CH004024 |
| Num Factors: | 2 |
| Num Metabolites: | 285 |
| Rt Units: | Minutes |
| Units: | pmol lipid per mg tissue |
| Analysis ID: | AN005321 |
| Analysis Type: | MS |
| Chromatography ID: | CH004025 |
| Num Factors: | 2 |
| Num Metabolites: | 253 |
| Rt Units: | Minutes |
| Units: | pmol lipid per mg tissue |
