title: Destabilization of the outer and inner mitochondrial membranes by core and linker histones.
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.
  
  
  RESULTS
  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.
authors.affiliation: Research Program Unit, Biomedicum Helsinki 1, University of Helsinki, Helsinki, Finland.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Cascone
authors.forename: Celine
authors.initials: C
authors.lastname: Bruelle
authors.forename: Dan
authors.initials: D
authors.lastname: Lindholm
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.forename: Ove
authors.initials: O
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D051381:Rats
chemical_list: D006657:Histones; D009243:NAD; D045304:Cytochromes c