Yale Researchers Uncover Coenzyme A Transport Mechanism into Mitochondria
Yale scientists have identified the transport system that moves Coenzyme A into mitochondria, resolving a longstanding biological question and offering insights into metabolic diseases.
Yale researchers have identified the transport system responsible for moving Coenzyme A (CoA) into mitochondria, resolving a longstanding question in cellular biology. CoA, derived from vitamin B5, is essential for metabolism, with up to 95% located within mitochondria.
The study, published in Nature Metabolism, reveals that CoA is imported into mitochondria through specific transport mechanisms. Senior author Hongying Shen, PhD, associate professor of cellular and molecular physiology at Yale School of Medicine, noted the challenge in studying CoA due to its tendency to bind with other molecules, forming various CoA conjugates.
To address this, Shen's team developed a mass spectrometry-based method to profile CoA conjugates, identifying 33 types in whole cells and 23 within mitochondria. They found that the enzyme responsible for CoA production is primarily located outside mitochondria. When cells lacked the transporters for CoA, mitochondrial CoA levels dropped significantly, indicating that these transporters are essential for CoA import.
Understanding this transport system provides insights into diseases linked to CoA dysfunction. Mutations in genes encoding CoA transporters have been associated with encephalomyopathy, a condition involving developmental delays, epilepsy, and reduced muscle tone. Additionally, mutations in enzymes involved in CoA production are linked to neurodegenerative diseases.
Shen and her colleagues are now investigating how mitochondrial CoA levels are regulated in specific cell types, such as neurons, and how dysregulation may contribute to disease. She emphasized the importance of understanding cellular metabolism to inform potential diagnostic and therapeutic strategies for metabolic and mitochondrial disorders.