Are Rod Outer Segment ATP-ase and ATP-Synthase Activity Expression of the Same Protein?

Abstract

Vertebrate retinal rod outer segments (OS) consist of a stack of disks surrounded by the plasma membrane, where phototransduction takes place. Energetic metabolism in rod OS remains obscure. Literature described a so-called Mg(2+)-dependent ATPase activity, while our previous results demonstrated the presence of oxidative phosphorylation (OXPHOS) in OS, sustained by an ATP synthetic activity. Here we propose that the OS ATPase and ATP synthase are the expression of the same protein, i.e., of F1Fo-ATP synthase. Imaging on bovine retinal sections showed that some OXPHOS proteins are expressed in the OS. Biochemical data on bovine purified rod OS, characterized for purity, show an ATP synthase activity, inhibited by classical F1Fo-ATP synthase inhibitors. Moreover, OS possess a pH-dependent ATP hydrolysis, inhibited by pH values below 7, suggestive of the functioning of the inhibitor of F1 (IF1) protein. WB confirmed the presence of IF1 in OS, substantiating the expression of F1Fo ATP synthase in OS. Data suggest that the OS F1Fo ATP synthase is able to hydrolyze or synthesize ATP, depending on in vitro or in vivo conditions and that the role of IF1 would be pivotal in the prevention of the reversal of ATP synthase in OS, for example during hypoxia, granting photoreceptor survival.

RETRACTED: ATPase inhibitory factor 1 is a prognostic marker and contributes to proliferation and invasion of human gastric cancer cells

“…IF1 specifically inhibits the ATP-hydrolyzing activity of the F1Fo-ATP synthase without impacting the synthesis of ATP during oxidative phosphorylation [17,18]. Elevated expression of IF1 has been observed in a number of human cancers [11][12][13].…”

Effect of polyphenolic phytochemicals on ectopic oxidative phosphorylation in rod outer segments of bovine retina

“…Having previously reported that ATP synthase and ATPase in the OS represent the same protein, that is the ectopic ATP synthase (Calzia et al ., ), ATPase activity was assayed in the presence of EGCG and quercetin to test their inhibitory action on OS ATP hydrolytic activity, as reported for mitochondrial ATP synthase (Zheng and Ramirez, ). As shown in Figure A and B, either compound exhibited concentration‐dependent inhibition of ATP hydrolysis.…”

Extramitochondrial energy production in platelets

“…On the other hand, in the last few years, several Authors have reported the extramitochondrial functional expression of the OXPHOS machinery [reviewed in Panfoli et al., ], indicating that mitochondrial proteins are exportable. An extramitochondrial OXPHOS was reported in rod outer segment disks [Panfoli et al., , ; Calzia et al., ], myelin sheath from both central and peripheral nervous system [Ravera et al., , , , , ,b], plasma membrane of glioma C6 cells [Ravera et al., ] and lung adenocarcinoma cells [Chang et al., ]. These data are supported by several proteomic analyses [reviewed in Panfoli et al., ].…”