Fig. 8

Dysregulation of the citric acid cycle in rods with chronically active HIFs. a,b Significantly downregulated citric acid cycle associated enzymes in photoreceptors segments (PS) or outer nuclear layer (ONL) of \(rod^{\varDelta \ Vhl}\) mice at 2.5 months of age. Protein levels are shown as boxplots with the median and 25% and 75% percentiles (a) or bar graphs representing normalized abundance ratios of \(rod^{\varDelta \ Vhl}\)/ctrl (b). N = 6 mice per genotype. The samples with the highest (red) and lowest (blue) Cre levels are indicated. For statistical analysis on proteomics data see Methods. nd, not detected. *: p \(\le\) 0.05. **: p \(\le\) 0.01. c Representation of the citric acid cycle with red arrows marking significantly downregulated proteins in the PRs of \(rod^{\varDelta \ Vhl}\) mice. d-f Representative immunofluorescence labeling for SDH subunit A (SDHA; d), citrate synthase (CS; e), and aconitate hydratase (ACO2; f) in the PS regions of \(rod^{\varDelta \ Vhl}\), \(rod^{\varDelta \ Cox10}\) and ctrl mice at time points as indicated (top panels). Pixel intensity (PI) profiles through the PS (bottom panels). White arrows: regions with reduced labeling. Scale bars, 50 \(\upmu\)m. N = 3 mice per genotype. g Dysregulation of OXPHOS and the TCA cycle in rods with chronic HIF activation is associated with impaired of OS biogenesis and leads to PRs degeneration