VDAC Genes Expression and Regulation in Mammals
VDACs are pore-forming proteins, coating the mitochondrial outer membrane, and playing the role of main regulators for metabolites exchange between cytosol and mitochondria. In mammals, three isoforms have evolutionary originated, VDAC1, VDAC2, and VDAC3. Despite similarity in sequence and structure...
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doaj-b8a439b313e7417e9edd94a0e4ee72542021-08-05T06:38:25ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-08-011210.3389/fphys.2021.708695708695VDAC Genes Expression and Regulation in MammalsFederica Zinghirino0Xena Giada Pappalardo1Angela Messina2Angela Messina3Giuseppe Nicosia4Vito De Pinto5Vito De Pinto6Vito De Pinto7Francesca Guarino8Francesca Guarino9Francesca Guarino10Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalySection of Molecular Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italywe.MitoBiotech.srl, Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italywe.MitoBiotech.srl, Catania, ItalySection of Catania, National Institute of Biostructures and Biosystems, Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italywe.MitoBiotech.srl, Catania, ItalySection of Catania, National Institute of Biostructures and Biosystems, Catania, ItalyVDACs are pore-forming proteins, coating the mitochondrial outer membrane, and playing the role of main regulators for metabolites exchange between cytosol and mitochondria. In mammals, three isoforms have evolutionary originated, VDAC1, VDAC2, and VDAC3. Despite similarity in sequence and structure, evidence suggests different biological roles in normal and pathological conditions for each isoform. We compared Homo sapiens and Mus musculus VDAC genes and their regulatory elements. RNA-seq transcriptome analysis shows that VDAC isoforms are expressed in human and mouse tissues at different levels with a predominance of VDAC1 and VDAC2 over VDAC3, with the exception of reproductive system. Numerous transcript variants for each isoform suggest specific context-dependent regulatory mechanisms. Analysis of VDAC core promoters has highlighted that, both in a human and a mouse, VDAC genes show features of TATA-less ones. The level of CG methylation of the human VDAC genes revealed that VDAC1 promoter is less methylated than other two isoforms. We found that expression of VDAC genes is mainly regulated by transcription factors involved in controlling cell growth, proliferation and differentiation, apoptosis, and bioenergetic metabolism. A non-canonical initiation site termed “the TCT/TOP motif,” the target for translation regulation by the mTOR pathway, was identified in human VDAC2 and VDAC3 and in every murine VDACs promoter. In addition, specific TFBSs have been identified in each VDAC promoter, supporting the hypothesis that there is a partial functional divergence. These data corroborate our experimental results and reinforce the idea that gene regulation could be the key to understanding the evolutionary specialization of VDAC isoforms.https://www.frontiersin.org/articles/10.3389/fphys.2021.708695/fullVDAC mammalian genesexpression profilegene structuremitochondriapromoter methylationcore promoter elements |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Federica Zinghirino Xena Giada Pappalardo Angela Messina Angela Messina Giuseppe Nicosia Vito De Pinto Vito De Pinto Vito De Pinto Francesca Guarino Francesca Guarino Francesca Guarino |
spellingShingle |
Federica Zinghirino Xena Giada Pappalardo Angela Messina Angela Messina Giuseppe Nicosia Vito De Pinto Vito De Pinto Vito De Pinto Francesca Guarino Francesca Guarino Francesca Guarino VDAC Genes Expression and Regulation in Mammals Frontiers in Physiology VDAC mammalian genes expression profile gene structure mitochondria promoter methylation core promoter elements |
author_facet |
Federica Zinghirino Xena Giada Pappalardo Angela Messina Angela Messina Giuseppe Nicosia Vito De Pinto Vito De Pinto Vito De Pinto Francesca Guarino Francesca Guarino Francesca Guarino |
author_sort |
Federica Zinghirino |
title |
VDAC Genes Expression and Regulation in Mammals |
title_short |
VDAC Genes Expression and Regulation in Mammals |
title_full |
VDAC Genes Expression and Regulation in Mammals |
title_fullStr |
VDAC Genes Expression and Regulation in Mammals |
title_full_unstemmed |
VDAC Genes Expression and Regulation in Mammals |
title_sort |
vdac genes expression and regulation in mammals |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2021-08-01 |
description |
VDACs are pore-forming proteins, coating the mitochondrial outer membrane, and playing the role of main regulators for metabolites exchange between cytosol and mitochondria. In mammals, three isoforms have evolutionary originated, VDAC1, VDAC2, and VDAC3. Despite similarity in sequence and structure, evidence suggests different biological roles in normal and pathological conditions for each isoform. We compared Homo sapiens and Mus musculus VDAC genes and their regulatory elements. RNA-seq transcriptome analysis shows that VDAC isoforms are expressed in human and mouse tissues at different levels with a predominance of VDAC1 and VDAC2 over VDAC3, with the exception of reproductive system. Numerous transcript variants for each isoform suggest specific context-dependent regulatory mechanisms. Analysis of VDAC core promoters has highlighted that, both in a human and a mouse, VDAC genes show features of TATA-less ones. The level of CG methylation of the human VDAC genes revealed that VDAC1 promoter is less methylated than other two isoforms. We found that expression of VDAC genes is mainly regulated by transcription factors involved in controlling cell growth, proliferation and differentiation, apoptosis, and bioenergetic metabolism. A non-canonical initiation site termed “the TCT/TOP motif,” the target for translation regulation by the mTOR pathway, was identified in human VDAC2 and VDAC3 and in every murine VDACs promoter. In addition, specific TFBSs have been identified in each VDAC promoter, supporting the hypothesis that there is a partial functional divergence. These data corroborate our experimental results and reinforce the idea that gene regulation could be the key to understanding the evolutionary specialization of VDAC isoforms. |
topic |
VDAC mammalian genes expression profile gene structure mitochondria promoter methylation core promoter elements |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2021.708695/full |
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