title: Increased mitochondrial respiratory chain enzyme activities correlate with minor extent of liver damage in mice suffering from erythropoietic protoporphyria.
abstract: Mitochondrial dysfunction might play a role in the pathogenesis of liver damage in erythropoietic protoporphyria (EPP). Changes in mitochondrial respiratory chain activities were evaluated in the Fech(m1pas)/Fech(m1pas) mouse model for EPP. Mice from different strains congenic for the same ferrochelatase germline mutation manifest variable degrees of hepatobiliary injury. Protoporphyric animals bred into the C57BL/6J background showed a higher degree of hepatomegaly and liver damage as well as higher protoporphyrin (PP) accumulation than those bred into the SJL/J and BALB/cJ backgrounds. Whereas mitochondrial respiratory chain activities remained unchanged in the liver of protoporphyric mice C57BL/6J, they were increased in protoporphyric mice from both SJL/J and BALB/cJ backgrounds, when compared to wild-type animals. Mitochondrial respiratory chain activities were increased in Hep G2 cell line after accumulation of PP following addition of aminolevulinic acid. As a direct effect of these elevated mitochondrial activities, in both hepatic cells from mutant mouse strains and Hep G2 cells, adenosine 5'-triphosphate (ATP) levels significantly increased as the intracellular PP concentration was reduced. These results indicate that PP modifies intracellular ATP requirements as well as hepatic mitochondrial respiratory chain enzymatic activities and further suggest that an increase of these activities may provide a certain degree of protection against liver damage in protoporphyric mice.
authors.affiliation: Centro de Investigación, Hospital 12 de Octubre, Avda. de Andalucía, Km 5.4, 28041 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Navarro
authors.forename: Pilar
authors.initials: P
authors.lastname: Del Hoyo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
authors.forename: Marie
authors.initials: M
authors.lastname: Abitbol
authors.forename: María-José
authors.initials: MJ
authors.lastname: Morán-Jiménez
authors.forename: María
authors.initials: M
authors.lastname: García-Bravo
authors.forename: Pilar
authors.initials: P
authors.lastname: Ochoa
authors.forename: Montserrat
authors.initials: M
authors.lastname: Grau
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.forename: Jorge
authors.initials: J
authors.lastname: Frank
authors.forename: Rafael
authors.initials: R
authors.lastname: Garesse
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Rafael Enríquez
authors.initials: RE
authors.lastname: de Salamanca
authors.forename: Antonio
authors.initials: A
authors.lastname: Fontanellas
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004579:Electron Transport; D005294:Ferrochelatase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D046351:Protoporphyria, Erythropoietic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011524:Protoporphyrins / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; D000255:Adenosine Triphosphate; D005294:Ferrochelatase