title: Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2.
abstract: Homozygous mice carrying kd (kidney disease) mutations in the gene encoding prenyl diphosphate synthase subunit 2 (Pdss2kd/kd) develop interstitial nephritis and eventually die from end-stage renal disease. The PDSS2 polypeptide in concert with PDSS1 synthesizes the polyisoprenyl tail of coenzyme Q (Q or ubiquinone), a lipid quinone required for mitochondrial respiratory electron transport. We have shown that a deficiency in Q content is evident in Pdss2kd/kd mouse kidney lipid extracts by 40 days of age and thus precedes the onset of proteinuria and kidney disease by several weeks. The presence of the kd (V117M) mutation in PDSS2 does not prevent its association with PDSS1. However, heterologous expression of the kd mutant form of PDSS2 together with PDSS1 in Escherichia coli recapitulates the Q deficiency observed in the Pdss2kd/kd mouse. Dietary supplementation with Q10 provides a dramatic rescue of both proteinuria and interstitial nephritis in the Pdss2kd/kd mutant mice. The results presented suggest that Q may be acting as a potent lipid-soluble antioxidant, rather than by boosting kidney mitochondrial respiration. Such Q10 supplementation may have profound and beneficial effects in treatment of certain forms of focal segmental glomerulosclerosis that mirror the renal disease of the Pdss2kd/kd mouse.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Saiki
authors.forename: Adam L
authors.initials: AL
authors.lastname: Lunceford
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Shi
authors.forename: Beth
authors.initials: B
authors.lastname: Marbois
authors.forename: Rhonda
authors.initials: R
authors.lastname: King
authors.forename: Justin
authors.initials: J
authors.lastname: Pachuski
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawamukai
authors.forename: David L
authors.initials: DL
authors.lastname: Gasser
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Clarke
mesh_terms: D000419:Albuminuria / Q000652:urine; D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D005260:Female; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009393:Nephritis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D021122:Protein Subunits; D014451:Ubiquinone; D019883:Alkyl and Aryl Transferases; C039821:decaprenyl pyrophosphate synthetase; C024989:coenzyme Q10; C030571:ubiquinone 9
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