1 / 14

Cardiolipin

Cardiolipin. Xi Huang Feb 3, 2009. Cardiolipin. Structure Biosynthesis and metabolism Function Cardiolipin in disease. Structure of Cardiolipin. Diphosphatidylglycerol 1,3- bis ( sn -3’-phosphatidyl)- sn -glycerol.

elsbeth
Download Presentation

Cardiolipin

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cardiolipin Xi Huang Feb 3, 2009

  2. Cardiolipin • Structure • Biosynthesis and metabolism • Function • Cardiolipin in disease

  3. Structure of Cardiolipin • Diphosphatidylglycerol 1,3-bis(sn-3’-phosphatidyl)-sn-glycerol • It’s usually found in certain membrane of bacteria and of mitochondria. • Itamounts to about 10% of the phospholipids of bovine heart muscle, and 20% of the phospholipidsof the mitochondrial membrane in this organ

  4. Structure of Cardiolipin ____________________________________________________________________________ Schlame, M., Brody, S. and Hostetler, K.Y. Eur. J. Biochem (2002) 528 35-39

  5. Acyl chain - 18:2 In heart mitochondria NAO pK1≈3, pK2＞7.5 Acid-anion bicyclic resonance structure One of the protons is trapped ____________________________________________________________________________ Thomas H. Hainesa;, Norbert A. Dencherb. (2002) FEBS Letters528 35-39

  6. Biosynthesis and metabolism Prokaryotic mechanism Eukaryotic mechanism

  7. PLD PLA2 PLA2 PLA2 PLD PLA2 PLA2 PLA2 Biosynthesis and metabolism

  8. Build quaternary structure 4 Fe 2+ -cytochrome c + 8 H+in + O2 → 4 Fe3+-cytochrome c + 2 H2O + 4 H+out Cytochrome c oxidase (Complex IV)need to form a dimer to catalysis the reaction. Cardiolipin help to connect the subunits with the complex Cytochrome bc1(Complex III) also need cardiolipin to maintain its quaternary structure

  9. Serve as proton trap for oxidative phosphorylation ____________________________________________________________________________ Thomas H. Hainesa;, Norbert A. Dencherb. (2002) FEBS Letters528 35-39

  10. Trigger apoptosis Cytochrome c released into cytosol react with IP3 receptor on ER  release calcium  large release of cytochrome c ____________________________________________________________________________ Natalia A. Belikova, Yury A. Vladimirov, at el. (2006) Biochemistry.45, 4998-5009

  11. Other Functions • cholesterol translocation from outer to the inner membrane of mitochondrial • activates mitochondrial cholesterol side-chain cleavage • Import protein into mitochondrial • anti-coagulant function …..

  12. Disease • Barth syndrome mutation in the gene coding for tafazzin  can’t synthesis enough cardiolipin  not enough ATP production • Diabetes  higher heart attack rate diabetes  more active lipid-digesting enzyme  quicker catabolism of cardiolipin  heart attack • Alzheimer’s disease and Parkinson’s disease Malfunction of cardiolipin metabolism in brain mitochondria

  13. Difficulties in neutralizing HIV-1 envelope Two antibodies directed against MPR, 2F5, 4E10, react with self-antigens, including cardiolipin Such antibodies would not be easily elicited by vaccination. ____________________________________________________________________________ Gary J. Nabel. (2005) Science. 308, 1878-1879

  14. Reference • Thomas H. Hainesa, Norbert A. Dencherb. (2002) FEBS Lett.528, 35-39 • Gary J. Nabel. (2005) Science. 308, 1878-1879 • Antonio Ortiz, J. Antoinette Killian, et al. (1999) Biophysical Journal.77, 2003–2014 • Mei Zhang, Eugenia Mileykovskaya and William Dowhan. (2002) J. Biol. Chem.277, 43553–43556 • Natalia A. Belikova, Yury A. Vladimirov, et al. (2006) Biochemistry.45, 4998-5009 • Valerian E Kagan, et al. (2005) Nat. Chem. Biol.1, 223-232 • Schlame, M., Brody, S. and Hostetler, K.Y. Eur. J. Biochem (2002) 528 35-39

More Related