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Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?

Authors :
Phoon, Nina Singh
Mindong Ren
Colin K. L.
Source :
Journal of Cardiovascular Development and Disease; Volume 10; Issue 4; Pages: 154
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

Background: Although the heart requires abundant energy, only 20–40% of children with mitochondrial diseases have cardiomyopathies. Methods: We looked for differences in genes underlying mitochondrial diseases that do versus do not cause cardiomyopathy using the comprehensive Mitochondrial Disease Genes Compendium. Mining additional online resources, we further investigated possible energy deficits caused by non-oxidative phosphorylation (OXPHOS) genes associated with cardiomyopathy, probed the number of amino acids and protein interactors as surrogates for OXPHOS protein cardiac “importance”, and identified mouse models for mitochondrial genes. Results: A total of 107/241 (44%) mitochondrial genes was associated with cardiomyopathy; the highest proportion were OXPHOS genes (46%). OXPHOS (p = 0.001) and fatty acid oxidation (p = 0.009) defects were significantly associated with cardiomyopathy. Notably, 39/58 (67%) non-OXPHOS genes associated with cardiomyopathy were linked to defects in aerobic respiration. Larger OXPHOS proteins were associated with cardiomyopathy (p < 0.05). Mouse models exhibiting cardiomyopathy were found for 52/241 mitochondrial genes, shedding additional insights into biological mechanisms. Conclusions: While energy generation is strongly associated with cardiomyopathy in mitochondrial diseases, many energy generation defects are not linked to cardiomyopathy. The inconsistent link between mitochondrial disease and cardiomyopathy is likely to be multifactorial and includes tissue-specific expression, incomplete clinical data, and genetic background differences.

Details

Language :
English
ISSN :
23083425
Database :
OpenAIRE
Journal :
Journal of Cardiovascular Development and Disease; Volume 10; Issue 4; Pages: 154
Accession number :
edsair.multidiscipl..edb4cace6e597c35b8ca367a0b60be2d
Full Text :
https://doi.org/10.3390/jcdd10040154