Destabilization of the Outer and Inner Mitochondrial Membranes by Core and Linker Histones

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Apr 24

PMID 22523586

Citations 16

Authors

Annunziata Cascone

Celine Bruelle

Dan Lindholm

Paolo Bernardi

Ove Eriksson

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methodology/principal Findings: 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.

Conclusions: We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage.

Citing Articles

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El-Ansary A, Alfawaz H, Ben Bacha A, Al-Ayadhi L Brain Sci. 2024; 14(6).

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Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury.

Yu J, Fu Y, Gao J, Zhang Q, Zhang N, Zhang Z Redox Biol. 2024; 74:103231.

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Extracellular histone release by renal cells after warm and cold ischemic kidney injury: Studies in an ex-vivo porcine kidney perfusion model.

van Smaalen T, Beurskens D, Kox J, Polonia R, Vos R, Duimel H PLoS One. 2023; 18(1):e0279944.

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The role of extracellular histones in COVID-19.

de Vries F, Huckriede J, Wichapong K, Reutelingsperger C, Nicolaes G J Intern Med. 2022; 293(3):275-292.

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Extracellular Histones Activate Endothelial NLRP3 Inflammasome and are Associated with a Severe Sepsis Phenotype.

Beltran-Garcia J, Osca-Verdegal R, Perez-Cremades D, Novella S, Hermenegildo C, Pallardo F J Inflamm Res. 2022; 15:4217-4238.

PMID: 35915852 PMC: 9338392. DOI: 10.2147/JIR.S363693.

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