In vitro interactions between the two mitochondrial membrane proteins VDAC and cytochrome c oxidase.
VDAC, a mitochondrial outer membrane channel, is involved in the control of aerobic metabolism and in apoptotic processes via numerous protein-protein interactions. To unveil those interactions, we screened a human liver cDNA library with the phage display methodology optimized to target VDAC reconstituted into a membrane environment. One positively selected clone yielded a sequence matching a part of the subunit I of human cytochrome c oxidase (COX), a mitochondrial inner membrane enzyme. Such putative interaction was never reported before. This interaction proved to be functional as evidenced by the effect of the human and yeast isoforms of VDAC on the oxidation of cytochrome c by the pure holoenzyme and by the effect of the COX epitope on VDAC permeability. Our results providing four independently obtained evidences of VDAC-COX interaction in vitro, would support a novel and potentially important level of mitochondrial regulation given the respective locations and functions of both proteins.
Roman
Inge
I
Department of Physiology, FYSP-Neurophysiology, Vrije Universiteit Brussel (VUB), Brussels 1090, Belgium.
Figys
Jurgen
J
Steurs
Griet
G
Zizi
Martin
M
D003576:Electron Transport Complex IV / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008099:Liver / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
D024101:Mitochondrial Proteins; D020033:Protein Isoforms; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1; D003576:Electron Transport Complex IV