title: The deactive form of respiratory complex I from mammalian mitochondria is a Na+/H+ antiporter.
abstract: In mitochondria, complex I (NADH:ubiquinone oxidoreductase) uses the redox potential energy from NADH oxidation by ubiquinone to transport protons across the inner membrane, contributing to the proton-motive force. However, in some prokaryotes, complex I may transport sodium ions instead, and three subunits in the membrane domain of complex I are closely related to subunits from the Mrp family of Na(+)/H(+) antiporters. Here, we define the relationship between complex I from Bos taurus heart mitochondria, a close model for the human enzyme, and sodium ion transport across the mitochondrial inner membrane. In accord with current consensus, we exclude the possibility of redox-coupled Na(+) transport by B. taurus complex I. Instead, we show that the "deactive" form of complex I, which is formed spontaneously when enzyme turnover is precluded by lack of substrates, is a Na(+)/H(+) antiporter. The antiporter activity is abolished upon reactivation by the addition of substrates and by the complex I inhibitor rotenone. It is specific for Na(+) over K(+), and it is not exhibited by complex I from the yeast Yarrowia lipolytica, which thus has a less extensive deactive transition. We propose that the functional connection between the redox and transporter modules of complex I is broken in the deactive state, allowing the transport module to assert its independent properties. The deactive state of complex I is formed during hypoxia, when respiratory chain turnover is slowed, and may contribute to determining the outcome of ischemia-reperfusion injury.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, United Kingdom.
authors.forename: Philippa G
authors.initials: PG
authors.lastname: Roberts
authors.forename: Judy
authors.initials: J
authors.lastname: Hirst
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D017136:Ion Transport; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D012964:Sodium / Q000737:chemistry* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000378:metabolism; D025062:Yarrowia / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D024101:Mitochondrial Proteins; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D042967:Electron Transport Complex I