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Cardiolipin
Xi Huang
Feb 3, 2009
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Cardiolipin
Structure Biosynthesis and metabolism Function Cardiolipin in disease
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Diphosphatidylglycerol 1,3-bis(sn-3’-phosphatidyl)-sn-glycerol
It’s usually found in certain membrane of bacteria and of mitochondria. It amounts to about 10% of the phospholipids of bovine heart muscle, and 20% of the
phospholipids of the mitochondrial membrane in this organ
Structure of Cardiolipin
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Structure of Cardiolipin
____________________________________________________________________________Schlame, M., Brody, S. and Hostetler, K.Y. Eur. J. Biochem (2002) 528 35-39
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Acyl chain - 18:2In heart mitochondria
pK1≈3, pK2> 7.5
Acid-anion bicyclic resonance structureOne of the protons is trapped
____________________________________________________________________________Thomas H. Hainesa;, Norbert A. Dencherb. (2002) FEBS Letters 528 35-39
N
10-N-Nonyl acridine
NAO
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Biosynthesis and metabolism
Eukaryotic mechanism
Prokaryotic mechanism
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Biosynthesis and metabolism
PLA2
PLA2
PLA2
PLA2
PLA2
PLA2
PLD
PLD
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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
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Serve as proton trap for oxidative phosphorylation
____________________________________________________________________________Thomas H. Hainesa;, Norbert A. Dencherb. (2002) FEBS Letters 528 35-39
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Trigger apoptosis
____________________________________________________________________________Natalia A. Belikova, Yury A. Vladimirov, at el. (2006) Biochemistry. 45, 4998-5009
Cytochrome c released into cytosol react with IP3 receptor on ER release calcium large release of cytochrome c
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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
…..
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Disease
Barth syndromemutation 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 cardiol
ipin heart attack
Alzheimer’s disease and Parkinson’s disease Malfunction of cardiolipin metabolism in brain mitochondria
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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
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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, 200
3–2014 Mei Zhang, Eugenia Mileykovskaya and William Dowhan. (2002) J. Biol. Ch
em. 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 35-3
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