title: Mitochondrial dysfunction in congenital nephrotic syndrome.
abstract: The molecular mechanisms maintaining the kidney glomerular filtration barrier remain poorly understood. Recent evidence suggests that mitochondrial dysfunction is a characteristic feature of kidney glomeruli in congenital nephrotic syndrome of the Finnish type (CNF). Here we searched for detailed functional evidence of mitochondrial lesion in CNF kidneys. We used histochemical and immunohistochemical methods, quantitative measurement of mitochondrial DNA, and superoxide production to characterize the mitochondrial function. The results unequivocally show down-regulation of mitochondria-encoded respiratory chain components, whereas the respective nuclearly encoded subunits were close to normal. These results give detailed evidence of distinct mitochondrial dysfunction and of the resulting abnormal production of reactive oxygen species in CNF and suggest a critical role for mitochondria in maintaining the glomerular permeability barrier.
authors.affiliation: Haartman Institute, Division of Bacteriology and Immunology, University of Helsinki, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Solin
authors.forename: S
authors.initials: S
authors.lastname: Pitkänen
authors.forename: J W
authors.initials: JW
authors.lastname: Taanman
authors.forename: H
authors.initials: H
authors.lastname: Holthöfer
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000378:metabolism / Q000503:physiopathology*; D017382:Reactive Oxygen Species; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013481:Superoxides; D013384:Succinate Cytochrome c Oxidoreductase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV