The molecular mechanisms maintaining the kidney glomerular filtration barri
er remain poorly understood. Recent evidence suggests that mitochondrial dy
sfunction is a characteristic feature of kidney glomeruli in congenital nep
hrotic syndrome of the Finnish type (CNF). Here we searched for detailed fu
nctional evidence of mitochondrial lesion in CNF kidneys. We used histochem
ical and immunohistochemical methods, quantitative measurement of mitochond
rial DNA, and superoxide production to characterize the mitochondrial funct
ion. The results unequivocally show down-regulation of mitochondria-encoded
respiratory chain components, whereas the respective nuclearly encoded sub
units were close to normal. These results give detailed evidence of distinc
t mitochondrial dysfunction and of the resulting abnormal production of rea
ctive oxygen species in CNF and suggest a critical role for mitochondria in
maintaining the glomerular permeability barrier.