Journal article
Mitoregulin supports mitochondrial membrane integrity and protects against cardiac ischemia-reperfusion injury
Cardiovascular research, Vol.122(3), pp.379-396
01/20/2026
DOI: 10.1093/cvr/cvag011
PMCID: PMC13019689
PMID: 41555203
Appears in UI Libraries Support Open Access
Abstract
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.
Details
- Title: Subtitle
- Mitoregulin supports mitochondrial membrane integrity and protects against cardiac ischemia-reperfusion injury
- Creators
- Colleen S Stein - University of IowaXiaoming Zhang - University of IowaNathan H Witmer - University of IowaEdward Ross Pennington - University of North Carolina at Chapel HillScott Hahn - University of PittsburghAdam C Straub - University of PittsburghSaame Raza Shaikh - University of North Carolina at Chapel HillRyan L Boudreau - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.122(3), pp.379-396
- DOI
- 10.1093/cvr/cvag011
- PMID
- 41555203
- PMCID
- PMC13019689
- NLM abbreviation
- Cardiovasc Res
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Publisher
- Oxford University Press
- Grant note
- American Heart Association: 23PRE1011277 University of Iowa Carver College of MedicineNIH NIDDK: P30DK056350 NIH NIGMS: T32GM067795 NIH NHLBI: R01HL144717, R01HL150557, R35HL177241, R35HL161177
This work was supported by the University of Iowa Carver College of Medicine (Distinguished Scholars Program to R.L.B.), NIH - National Heart, Lung, and Blood Institute (R01HL144717, R01HL150557, and R35HL177241 to R.L.B. and R35HL161177 to A.C.S.), NIH - National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056350 to S.R.S), NIH - National Institute of General Medical Sciences (predoctoral fellowship T32GM067795 to N.H.W), and the American Heart Association (23PRE1011277 to N.H.W.).
- Language
- English
- Electronic publication date
- 01/20/2026
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9985130061102771
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