Article

Cardiolipin stabilizes respiratory chain supercomplexes.

Zentrum der Biologischen Chemie, Universitätsklinikum Frankfurt, D-60590 Frankfurt, Germany.
Journal of Biological Chemistry (Impact Factor: 4.65). 01/2004; 278(52):52873-80. DOI: 10.1074/jbc.M308366200
Source: PubMed

ABSTRACT Cardiolipin stabilized supercomplexes of Saccharomyces cerevisiae respiratory chain complexes III and IV (ubiquinol:cytochrome c oxidoreductase and cytochrome c oxidase, respectively), but was not essential for their formation in the inner mitochondrial membrane because they were found also in a cardiolipin-deficient strain. Reconstitution with cardiolipin largely restored wild-type stability. The putative interface of complexes III and IV comprises transmembrane helices of cytochromes b and c1 and tightly bound cardiolipin. Subunits Rip1p, Qcr6p, Qcr9p, Qcr10p, Cox8p, Cox12p, and Cox13p and cytochrome c were not essential for the assembly of supercomplexes; and in the absence of Qcr6p, the formation of supercomplexes was even promoted. An additional marked effect of cardiolipin concerns cytochrome c oxidase. We show that a cardiolipin-deficient strain harbored almost inactive resting cytochrome c oxidase in the membrane. Transition to the fully active pulsed state occurred on a minute time scale.

0 Bookmarks
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activity and stability of life-supporting proteins are determined not only by their abundance and by post-translational modifications, but also by specific protein-protein interactions. This holds true both for signal-transduction and energy-converting cascades. For vital processes such as life-span control and senescence, to date predominantly age-dependent alterations in abundance and to lesser extent in post-translational modifications of proteins are examined to elucidate the cause of ageing at the molecular level. In mitochondria of rat cortex, we quantified profound changes in the proportion of supramolecular assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS electrophoresis and fluorescent staining. Complex I was present solely in supercomplexes and those lacking complex IV were least stable in aged animals (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age-associated degradation by an overall decline in abundance of 1.5-fold for the monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation.
    Experimental gerontology 02/2010; 45(7-8):563-72. · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiolipin is a unique phospholipid which is almost exclusively located in the inner mitochondrial membrane where it is biosynthesized. Considerable progress has recently been made in understanding the role of cardiolipin (CL) in mitochondrial function and bioenergetics. This phospholipid is associated with membranes designed to generate an electrochemical gradient that is used to produce ATP, such as bacterial plasma membranes and inner mitochondrial membrane (IMM). This ubiquitous and intimate association between CL and energy transducing membranes indicates an important role for CL in mitochondrial bioenergetic processes. Cardiolipin has been shown to interact with a number of IMM proteins, including the respiratory chain complexes and substrate carrier proteins. Over the past decade, the significance of CL in the organization of components of the electron transport chain into higher order assemblies, termed respiratory supercomplexes, has been established. Moreover, CL is involved in different stages of the mitochondrial apoptotic process, as well as in mitochondrial membrane stability and dynamics. This review discusses the current understanding of the functional role that CL plays in several reactions and processes involved in mitochondrial bioenergetics. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.
    Biochimica et Biophysica Acta 10/2013; · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiolipin (CL) is a class of phospholipid tightly associated with the mitochondria functions and a prime target of oxidative stress. Peroxidation of CL dissociates its bound cytochrome C, a phenomenon that reflects oxidative stress sustained by the organ and a trigger for the intrinsic apoptotic pathway. However, CL distribution in normal organ tissues has yet to be documented. Fresh rat organs were snap-frozen, cut into cryosections that were subsequently desalted with ammonium acetate solution, and vacuum-dried. CL distribution in situ was determined using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique on sections sublimed with 2,5-dihydroxybenzoic acid. CL images in rat cardiac ventricular section showed a homogeneous distribution of a single m/z 1447.9 ion species that was confirmed as the (18:2)4 CL by tandem mass spectrometry. The presence of low abundant (18:2)3(18:1) CL with the bulk (18:2)4 CL in quadriceps femoris rendered the muscle CL exhibiting a slightly deviated isotopic pattern from that of cardiac muscle. In rat liver, MALDI-MSI unveiled three CL-containing mass ranges, each with a unique in situ distribution pattern. Co-registration of the CL ion images with its stained liver section image further revealed the association of CLs in each mass range with the functional zones in the liver parenchyma and suggests the participation of in situ CLs with localized hepatic functions such as oxidation, conjugation, and detoxification. The advances in CL imaging offer an approach with molecular accuracy to reveal potentially dysregulated metabolic machineries in acute and chronic diseased states.
    Analytical and Bioanalytical Chemistry 12/2013; · 3.66 Impact Factor