Mitochondrial alterations in fanconi anemia fibroblasts following ultraviolet A or psoralen photoactivation.
The genetic disease Fanconi anemia (FA), generally considered to be a DNA repair defect, has also been related to a deficiency in cellular defense against reactive oxygen species (ROS). Results show that mitochondrial matrix densification occurs rapidly and transiently in FA fibroblasts following 8-methoxypsoralen (8-MOP) photoreaction or ultraviolet A (320 to 380 nm) (UVA) irradiation. This effect is oxygen dependent because it is more important under 20 than under 5% oxygen tension. In contrast, in normal fibroblasts very little, if any, densification of mitochondrial matrix is induced by treatments even at the highest oxygen tension. The changes in matrix density in FA cells are accompanied by some modifications in transmembrane potential, linked to a Fenton-like reaction, and in mitochondrial cardiolipin content, differing from the responses of normal cells. These data are indicative of some sort of membrane damage induced by 8-MOP photoreaction and UVA irradiation, to which FA cells appear to be particularly sensitive.
Rousset
Solange
S
UMR 218 CNRS, Institut Curie-Recherche, Paris, France. solange.rousset@curie.u-psud.fr
Nocentini
Silvano
S
Rouillard
Danièlie
D
Baroche
Christiane
C
Moustacchi
Ethel
E
D002460:Cell Line; D005199:Fanconi Anemia / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology; D008928:Mitochondria / Q000473:pathology / Q000528:radiation effects*; D010100:Oxygen / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D017319:Photosensitizing Agents; D010100:Oxygen; D008730:Methoxsalen