Destabilization of the outer and inner mitochondrial membranes by core and linker histones.

<h4>Background</h4>Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria.<h4>Methodology/principal findings</h4>We have investigated the effects of...

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Autores principales:	Annunziata Cascone, Celine Bruelle, Dan Lindholm, Paolo Bernardi, Ove Eriksson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db81b922028b4698be8b8a5c99af8b66
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spelling	oai:doaj.org-article:db81b922028b4698be8b8a5c99af8b662021-11-18T07:22:02ZDestabilization of the outer and inner mitochondrial membranes by core and linker histones.1932-620310.1371/journal.pone.0035357https://doaj.org/article/db81b922028b4698be8b8a5c99af8b662012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22523586/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria.<h4>Methodology/principal findings</h4>We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation.<h4>Conclusions</h4>We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage.Annunziata CasconeCeline BruelleDan LindholmPaolo BernardiOve ErikssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35357 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annunziata Cascone Celine Bruelle Dan Lindholm Paolo Bernardi Ove Eriksson Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
description	<h4>Background</h4>Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria.<h4>Methodology/principal findings</h4>We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation.<h4>Conclusions</h4>We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage.
format	article
author	Annunziata Cascone Celine Bruelle Dan Lindholm Paolo Bernardi Ove Eriksson
author_facet	Annunziata Cascone Celine Bruelle Dan Lindholm Paolo Bernardi Ove Eriksson
author_sort	Annunziata Cascone
title	Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
title_short	Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
title_full	Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
title_fullStr	Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
title_full_unstemmed	Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
title_sort	destabilization of the outer and inner mitochondrial membranes by core and linker histones.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/db81b922028b4698be8b8a5c99af8b66
work_keys_str_mv	AT annunziatacascone destabilizationoftheouterandinnermitochondrialmembranesbycoreandlinkerhistones AT celinebruelle destabilizationoftheouterandinnermitochondrialmembranesbycoreandlinkerhistones AT danlindholm destabilizationoftheouterandinnermitochondrialmembranesbycoreandlinkerhistones AT paolobernardi destabilizationoftheouterandinnermitochondrialmembranesbycoreandlinkerhistones AT oveeriksson destabilizationoftheouterandinnermitochondrialmembranesbycoreandlinkerhistones
_version_	1718423566607712256

Destabilization of the outer and inner mitochondrial membranes by core and linker histones.

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