title: NO binding to the proapoptotic cytochrome c-cardiolipin complex.
abstract: Cytochrome c is a heme protein that is localized in the compartment between the inner and outer mitochondrial membranes where it functions to transfer electrons between complex III and complex IV of the respiratory chain. It can also form an intimate association with the mitochondrion-specific phospholipid cardiolipin that induces a conformational change in the protein enabling it to act as a peroxidase catalyzing the oxidation of cardiolipin and thereby instigating a chain of events that leads to apoptosis. Unlike the native protein, cytochrome c within the complex binds ligands rapidly; in particular, NO can coordinate to either the ferric or ferrous iron of the heme. Remarkably, in the ferrous form, NO binds preferentially to the proximal side of the heme and thus behaves in a way similar to cytochrome c'-type proteins and to guanylate cyclase. The implications of NO binding to the proapoptotic cytochrome c/cardiolipin complex are discussed in terms of modulating the apoptotic response and buffering NO concentrations. Insights into the structure of the complex are provided by comparison with cytochrome c' for which X-ray structures are available.
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hough
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Silkstone
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: J A R
authors.initials: JA
authors.lastname: Worrall
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom. Electronic address: wilsmt@essex.ac.uk.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wilson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002308:Cardiolipins; D009569:Nitric Oxide; D045304:Cytochromes c
keywords: Apoptosis; Cardiolipin; Cytochrome c′; Proximal binding; Soluble guanylate cyclase