RT Journal Article
T1 CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway.
A1 Kleiner, Giulio
A1 Barca, Emanuele
A1 Ziosi, Marcello
A1 Emmanuele, Valentina
A1 Xu, Yimeng
A1 Hidalgo-Gutierrez, Agustin
A1 Qiao, Changhong
A1 Tadesse, Saba
A1 Area-Gomez, Estela
A1 Lopez, Luis C
A1 Quinzii, Catarina M
K1 CoQ deficiency
K1 Coenzyme Q(10)
K1 Mitochondria
K1 Oxidative stress
K1 Sulfides
AB Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q10 (CoQ10) deficiency and is very responsive to CoQ10 supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ10 supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ10 supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ10 antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.
YR 2018
FD 2018-09-06
LK http://hdl.handle.net/10668/12994
UL http://hdl.handle.net/10668/12994
LA en
DS RISalud
RD Apr 7, 2025