Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts

Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiom...

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Main Authors: Williams, Jack L., Hall, Charlotte L., Meimaridou, Eirini, Metherell, Louise A.
Format: Article
Language:English
Published: MDPI 2021
Subjects:
Online Access:https://repository.londonmet.ac.uk/6737/1/ijms-22-06101.pdf
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author Williams, Jack L.
Hall, Charlotte L.
Meimaridou, Eirini
Metherell, Louise A.
author_facet Williams, Jack L.
Hall, Charlotte L.
Meimaridou, Eirini
Metherell, Louise A.
author_sort Williams, Jack L.
collection LMU
description Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts, adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J, which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However, differential gene expression was mainly driven by mouse background with some changes seen in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and -6N substrains.
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spelling oai:repository.londonmet.ac.uk:67372024-12-19T09:56:40Z https://repository.londonmet.ac.uk/6737/ Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts Williams, Jack L. Hall, Charlotte L. Meimaridou, Eirini Metherell, Louise A. 570 Life sciences; biology 610 Medicine & health Nicotinamide nucleotide transhydrogenase (NNT) is a proton pump in the inner mitochondrial membrane that generates reducing equivalents in the form of NAPDH, which can be used for anabolic pathways or to remove reactive oxygen species (ROS). A number of studies have linked NNT dysfunction to cardiomyopathies and increased risk of atherosclerosis; however, biallelic mutations in humans commonly cause a phenotype of adrenal insufficiency, with rare occurrences of cardiac dysfunction and testicular tumours. Here, we compare the transcriptomes of the hearts, adrenals and testes from three mouse models: the C57BL/6N, which expresses NNT; the C57BL/6J, which lacks NNT; and a third mouse, expressing the wild-type NNT sequence on the C57BL/6J background. We saw enrichment of oxidative phosphorylation genes in the C57BL/B6J in the heart and adrenal, possibly indicative of an evolved response in this substrain to loss of Nnt. However, differential gene expression was mainly driven by mouse background with some changes seen in all three tissues, perhaps reflecting underlying genetic differences between the C57BL/B6J and -6N substrains. MDPI 2021 Article PeerReviewed text en cc_by_4 https://repository.londonmet.ac.uk/6737/1/ijms-22-06101.pdf Williams, Jack L., Hall, Charlotte L., Meimaridou, Eirini and Metherell, Louise A. (2021) Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts. International Journal of Molecular Sciences, 22 (11). pp. 6101-6113. ISSN 1422-0067 https://doi.org/10.3390/ijms22116101 10.3390/ijms22116101 10.3390/ijms22116101
spellingShingle 570 Life sciences; biology
610 Medicine & health
Williams, Jack L.
Hall, Charlotte L.
Meimaridou, Eirini
Metherell, Louise A.
Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title_full Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title_fullStr Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title_full_unstemmed Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title_short Loss of NnT increases expression of oxidative phosphorylation complexes in C57BL/6J hearts
title_sort loss of nnt increases expression of oxidative phosphorylation complexes in c57bl 6j hearts
topic 570 Life sciences; biology
610 Medicine & health
url https://repository.londonmet.ac.uk/6737/1/ijms-22-06101.pdf
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