Updated project metadata. The retinal rod outer segment (OS) isa stack of diskssurrounded by the plasma membrane,housing proteins related to phototransduction as well asmitochondrial proteins involved in oxidative phosphorylation (OxPhos). This prompted us to compare the proteome of bovine OS disks and mitochondria, to assess the significant top gene signatures of each sample.The two proteomes, obtained byLTQ-OrbitrapVelos mass spectrometry, were compared by statistical analyses. 4139 proteins were identified, 2045 of which overlapping in the two sets. Non-hierarchical Spearman’s correlogram revealed that the groups were clearly discriminated. Partial Least Square Discriminant plus Support Vector Machine analysis identified the major discriminative proteins, implied in photo-transduction and lipid metabolism, respectively. Gene ontology analysis identified top gene signatures of disk proteome, enriched in vesiculation, glycolysis, and OxPhos proteins. The tricarboxylic acid (TCA) cycle and the electron transport proteinswere similarly enriched in the two samples: Notably thelatterwas up regulated in disks.Data suggest that the OxPhos proteins may derive from mitochondria becoming a true OS component, and acquiring different functionality once in ectopic location. Understanding theyet unanswered issue of chemical energy supply in the rod OS, can positively influence our vision of retinal physiology and pathology.