New Research Reveals the Molecular Mechanism of Cardiolipin

Cardiolipin is a unique phospholipid with a very interesting chemical and specific ultrastructural characteristics. In a research report published in the journal Science Advances in 28 Aug 2020, scientists from Johns Hopkins University and other institutions studied yeast and revealed the molecular mechanism of the fatty compound cardiolipin that helps produce cellular energy. This related research results are expected to help clarify the pathogenesis of diseases that affect human metabolism, such as heart disease, diabetes, and Bath syndrome. Cardiolipin is present in almost every cell of the body. It is located in the maze of cell membranes that make up mitochondria. It is believed to help mitochondria produce mitochondria create adenosine triphosphate (ATP), which is a special molecule that can induce cell metabolism. Now researchers have discovered that cardiolipin may be involved in the occurrence of a variety of body metabolism and immune diseases, including blood coagulation disorders caused by abnormal immune responses to lipid molecules. In this study, the researchers revealed how cardiolipin stabilizes other structures in the mitochondrial membrane. Professor Steven Claypool, one of the researcher at the Johns Hopkins University School of Medicine, explained that the mitochondrial membranes are one of the busiest structures in the body, which are rich in lipids and proteins and can provide the body’s cells with the energy needed to maintain life. There is an important transport protein called Aac2 in this membrane matrix, which can move the basic components of ATP into the mitochondria, and then remove the activated ATP molecules out of the cell. Previous studies have shown that cardiolipin plays an important role in helping the Aac2 transport, yet the specific details of the process are poorly understood. Now the researchers have found that cardiolipin can bind to the upper region on Aac2 to help it maintain the correct shape to transport ATP; and yeast cells modified to lack cardiolipin may not be able to produce cellular energy as efficiently as yeast cells with rich cardiolipin levels. When the researchers analyzed the interaction mechanism between the protein and the mitochondrial membrane in depth, they found that the relationship between Aac2 and the rest of the ATP production line (respiratory supercomplexes) may depend on the presence of cardiolipin. The researchers speculate that the phospholipid-protein interaction in the center of the mitochondrial membrane may continue to evolve as a way to simplify energy production. This is done by connecting Aac2 with the respiratory supercomplexes that supply ATP materials , or by using cardiolipin to protect membrane proteins from being squeezed. The results of this research show that changes in the structure or production of cardiolipin may be directly related to the occurrence of diseases. The researchers also expressed that they need to further study the structure and production mechanism of cardiolipin during disease occurrence (cardiolipin metabolism may be involved). Researcher Claypool said that they are currently developing new tools to analyze the lipids in the mitochondrial membrane to study the protein-cardiolipin interaction in more depth.