Summary of Study ST003246

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.

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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.

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Study IDST003246
Study TitleEffects of mitoregulin loss on cardiac and mitochondrial lipids in aged male mice
Study SummaryCardiac lipidome analysis in aged (21 to 23-months old) male wildtype and mtln knockout mice
Institute
University of Iowa
Last NameBoudreau
First NameRyan
Address4334 PBDB, 169 Newton Rd, Iowa City, IA 52242
Emailryan-boudreau@uiowa.edu
Phone3193535573
Submit Date2024-06-02
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-12-31
Release Version1
Ryan Boudreau Ryan Boudreau
https://dx.doi.org/10.21228/M81C00
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
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