Johns Hopkins Medicine scientists have discovered that biochemical bonds between fats and proteins in the mitochondria of yeast and human cells play a critical role in how cells produce energy. Published in The EMBO Journal, the study focuses on the altered mitochondrial membranes seen in individuals with metabolic diseases like Barth syndrome, which impacts heart function. Metabolism is essential for energy production and waste removal within the body, affecting one in three adults with conditions like high cholesterol.
The research builds upon previous studies and aims to understand the interaction between cardiolipin, a lipid, and proteins responsible for transporting ATP, an energy molecule made by mitochondria. According to senior author Steven Claypool, a better understanding of protein-lipid interactions could help identify new therapeutic targets for metabolic diseases. The experiments involved yeast samples with mutations in a protein called AAC, equivalent to human protein ANT, as well as human cell models mimicking mutations in protein ANT1 associated with metabolic disease symptoms.
By disrupting the interaction between cardiolipin and AAC in yeast, researchers found that the protein’s structure and function weakened, affecting its ability to bond with the lipid. Similarly, in the cell model representing mutations in protein ANT1, ATP transport across the mitochondrial membrane was compromised due to weakened protein structure. These findings suggest that breakdowns in protein-lipid interactions can disrupt the energy production process within mitochondria, impacting overall cell function.
The study highlights the importance of protein-lipid interactions in mitochondrial membranes, which contain numerous proteins associated with lipids. Claypool notes that few studies have explored individual protein-lipid interactions, necessitating further research to fully understand their roles and mechanisms within the membrane. The discovery offers new possibilities for unraveling the complexities of cellular energy production, prompting future investigations into other protein-lipid interactions contributing to this process.
This research involved a collaborative effort between multiple scientists from Johns Hopkins University, University of Oxford, and University of Connecticut, supported by funding from the National Institutes of Health, American Heart Association, Barth Syndrome Foundation, and other organizations. This study sheds light on the intricate relationship between fats and proteins in mitochondria, providing insights into metabolic diseases like Barth syndrome and potentially uncovering therapeutic targets for improved treatment outcomes. By delving into protein-lipid interactions, scientists hope to expand our understanding of energy production mechanisms within cells, paving the way for innovative approaches to addressing metabolic disorders.