Novel lipid transfer property of two mitochondrial proteins that bridge the inner and outer membranes.
This study provides evidence of a novel function for mitochondrial creatine kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D). Both are basic peripheral membrane proteins with symmetrical homo-oligomeric structure, which in the case of MtCK was already shown to allow crossbridging of lipid bilayers. Here, different lipid dilution assays clearly demonstrate that both kinases also facilitate lipid transfer from one bilayer to another. Lipid transfer occurs between liposomes mimicking the lipid composition of mitochondrial contact sites, containing 30 mol % cardiolipin, but transfer does not occur when cardiolipin is replaced by phosphatidylglycerol. Ubiquitous MtCK, but not NDPK-D, shows some specificity in the nature of the lipids transferred and it is not active with phosphatidylcholine alone. MtCK can undergo reversible oligomerization between dimeric and octameric forms, but only the octamer can bridge membranes and promote lipid transfer. Cytochrome c, another basic mitochondrial protein known to bind to anionic membranes but not crosslinking them, is also incapable of promoting lipid transfer. The lipid transfer process does not involve vesicle fusion or loss of the internal contents of the liposomes.
Epand
Raquel F
RF
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. epand@mcmaster.ca
Schlattner
Uwe
U
Wallimann
Theo
T
Lacombe
Marie-Lise
ML
Epand
Richard M
RM
D002308:Cardiolipins / Q000737:chemistry; D052281:Creatine Kinase, Mitochondrial Form / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry*; D009701:Nucleoside-Diphosphate Kinase / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation
D002308:Cardiolipins; D008055:Lipids; D008081:Liposomes; D024101:Mitochondrial Proteins; D045304:Cytochromes c; D052281:Creatine Kinase, Mitochondrial Form; D009701:Nucleoside-Diphosphate Kinase