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Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?

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 G...

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Autores principales: Singh, Nina, Ren, Mindong, Phoon, Colin K. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144188/
https://www.ncbi.nlm.nih.gov/pubmed/37103033
http://dx.doi.org/10.3390/jcdd10040154
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author Singh, Nina
Ren, Mindong
Phoon, Colin K. L.
author_facet Singh, Nina
Ren, Mindong
Phoon, Colin K. L.
author_sort Singh, Nina
collection PubMed
description 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.
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spelling pubmed-101441882023-04-29 Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy? Singh, Nina Ren, Mindong Phoon, Colin K. L. J Cardiovasc Dev Dis Article 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. MDPI 2023-04-01 /pmc/articles/PMC10144188/ /pubmed/37103033 http://dx.doi.org/10.3390/jcdd10040154 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Singh, Nina
Ren, Mindong
Phoon, Colin K. L.
Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title_full Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title_fullStr Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title_full_unstemmed Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title_short Why Don’t More Mitochondrial Diseases Exhibit Cardiomyopathy?
title_sort why don’t more mitochondrial diseases exhibit cardiomyopathy?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144188/
https://www.ncbi.nlm.nih.gov/pubmed/37103033
http://dx.doi.org/10.3390/jcdd10040154
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