title: Multiphoton imaging reveals differences in mitochondrial function between nephron segments.
abstract: Mitochondrial dysfunction may play a role in the pathogenesis of several renal diseases. Although functional roles and metabolic demands differ among tubule segments, relatively little is known about the properties of mitochondria in different parts of the nephron. Clinically, the proximal tubule seems particularly vulnerable to mitochondrial toxicity. In this study, we used multiphoton imaging of live rat kidney slices to investigate differences in mitochondrial function along the nephron. The mitochondrial membrane potential was markedly higher in distal than proximal tubules. Inhibition of respiration rapidly collapsed the membrane potential in proximal tubules, but potential was better maintained in distal tubules. Inhibition of the F1F(o)-ATPase abolished this difference, suggesting that maintenance of potential via ATPase activity is more effective in distal than proximal tubules. Immunostaining revealed that the ratio of the expression of ATPase to IF1, an endogenous inhibitor of the mitochondrial ATPase, was lower in proximal tubules than in distal tubules. Production of reactive oxygen species was higher in proximal than distal cells, but inhibition of NADPH oxidase eliminated this difference. Glutathione levels were higher in proximal tubules. Overall, mitochondria in the proximal tubules were in a more oxidized state than those in the distal tubules. In summary, there are axial differences in mitochondrial function along the nephron, which may contribute to the pattern and pathophysiology of some forms of renal injury.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK. andrew.hall@ucl.ac.uk
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Unwin
authors.forename: Nadeene
authors.initials: N
authors.lastname: Parker
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D036641:Microscopy, Fluorescence, Multiphoton; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000097795:ATPase Inhibitory Protein
chemical_list: D025261:Mitochondrial Proton-Translocating ATPases; D011506:Proteins; D017382:Reactive Oxygen Species; D000097795:ATPase Inhibitory Protein