cardiolipin

Cardiolipin or precisely 1,3-bis(sn-3′-phosphatidyl)-sn-glycerol is a very important part of mitochondria. It is a phoshlipid with a dimeric structure, having four acyl groups and potentially carrying two negative charges. It is found mostly in the mammalian heart than the rest of the organs.

Cardiolipin is part of the normal plasma lipo-proteins. Traditionally it was not considered to be a part of the plasma lipoprotein, but recent research has proved otherwise . It is located on the inner membrane of the mitochondria where it takes part in activation of enzymes involved in oxidative phosphyrlation. Cardiolipin is identified as a integral part of the respiratory chain and it forms a part of the crystals of mitochondrial complex III, complex IV and the ADP-ATP-carrier, and it is known to be essential for the stability of the quaternary protein structure of the last stage which results in ATP production, which is very essential for the cell to function .

It is a known fact that cardiolipins play a active role in oxidative phosphorylation mechanisms that regulate Stage 4 respiratory cycle by returning ejected protons across and over bacterial and mitochondrial membrane phospholipids, and that regulates State 3 respiration through the relative contributions of proteins that transport protons, electrons and/or metabolites. The barrier properties of phospholipid bilayers support and regulate the slow proton leak that is the basis for State 4 respiration. Mitochondrial cardiolipins, especially those with high 18:2 acyl contents, strongly bind many carrier and enzyme proteins that are involved in oxidative phosphorylation, some of which contribute to regulation of State 3 respiration. Role in Parkinson’s disease.

Role in Parkinsons Disease

Parkinson’s disease could be of two etiologies-1) Vascular 2) Death or depletion of dopaminergic neurons in Substantia Nigra. Cardiolipin is part of the HDL cholesterol and it and enhances the anticoagulation activities of plasma proteins S and activated protein C and would prevent Parkinsons of vascular etiology 4. The most important complex that gets destroyed in the substantia Niagra is CQ 10 (Co-Enzyme Q 10Complex) which is found in the mitochondria along with cardiolipin . The destruction of CQ10 would be reduced if the ample amount of cardiolipin is available. Since cardiolipin forms a component of Complex 3 and Complex 4, it will get oxidized first rather than CQ10. The mitochondria can then replace the cardiolipin needed for Complex3 and Complex 4 from the blood. This will slow down the apoptosis and slow down the progress of disease. Administering CQ 10 has potential side effects as it can be a source of superoxide radicals. At current, treating Parkinsons with CQ10 is not a standard treatment.A combination of CQ10 in appropriate doses and the newly developed cardiolipin analogue could prevent Parkinson’s disease in those with family history of the disease and stop the progression in those with the disease. There have been no studies at present that have either monitored the improvement of Parkinsons disease after administering CQ10. There is also new evidence that destruction of cardiolipin in brain cells result in brain tumors .

Role in Cardiac Disease

Cardiolipin is found the most in the heart. With forming the integral structures of the mitochondria of cardiac myocyte, it increases the efficiency of the heart as whole and improves it function. By its anti-coagulating effect in combination with Protein C and Protein S, it would prevent Ischemic Heart Disease . Cardiolipin is beneficial in maintaining the functions of the cardiac myocyte by ejecting protons across the barrier, facilitating its leak back into the matric which results in the production of ATP, stabilizing the structure of the phospholiping bilayer of the mitchondria. Any cell that has enough energy(ATP0) is able to maintain its function. By having adequate supply of cardiolipin, the function of the heart will improve and may prevent ischemic heart disease. The future protocol for management of IHD disease would definitely include a Cardiolipin analogue and CQ 10 along with the regular regimen of drugs used for treatment.

Most alcoholics though they have dilated cardiomyopathy and wernicke’s encephalopathy, do not have IHD and Parkinson’s Disease. Cardiolipins are by-products of the alcohol metabolism and alcoholics benefit from this protective qualities of cardiolipin.

Future Role of Cardiolipin

In the recent future, Cardiolipin will be used to treat Ischemic heart disease, there is a analogue already produced, but it has not been tried in Human subjects. It will be used in conjunction with CQ-10 and Ubiquinine to treat nuerological degenerative disease including Parkinsons and IHD.

Figure 1. Cytochrome c release from mitochondria. Cytochrome c (◯) is normally associated with cardiolipin on the inner mitochondrial membrane. Cytochrome c is dissociated upon oxidation of cardiolipin and is believed to be released out of mitochondria either by mitochondrial permeability transition resulting in mitochondrial swelling and rupture of the outer membrane, or by channels formed by oligomerization of Bax. In the cytoplasm, cytochrome c activates caspase-9 and promotes apoptosis.

Has this idea been thought of before in Medicine?

No, not as a treatment option. People normally focus on the HDL cholestrol and associate it to the benefit it has on the heart. Cardiolipin is the component in HDL which is responsible for this beneficial role. Giving Cardio-lipin directly will have more beneficial than trying to increase the HDL level. There needs to be further studies that need to be done on the effect of gastric enzymes on Cardio-lipin analogue when take orally and its further metablism by the Liver. Study done by CDC of Cardiolipin on lab mice showed that they more agile and alert and healthy than the counter parts without the cardiolipin supplement. They did not look into its nuerological benefits and cardiac benefits.

Cardiolipin may be used in anti-aging therapy in the future. As a cell that has a good supply of ATP will less likely degenerate to a point where the apoptosis gene/mechanism will be triggered. The life span of cells in the body are increased, which will lead to overall youthfullness and health. The time it will take for Cardio-lipin focussed treatment to come in the main stream will be another ten years. But for now, the medical society should acknowledge that Cardio-lipin has a important future role in IHD and Parkinsons disease.