Researchers Solve Mystery of Vitamin B5 Molecule Fueling Cellular Energy

Scientists have discovered how a vital molecule derived from Vitamin B5 reaches the energy-producing centers of cells, solving a long-standing biological mystery. The study, conducted by researchers at Yale University, was published in Nature Metabolism.

The molecule, known as Coenzyme A (CoA), plays a crucial role in metabolism—the network of chemical reactions that keep cells functioning. CoA helps activate and transport molecules involved in energy production and other essential metabolic processes. Interestingly, about 95% of CoA is found inside mitochondria, the structures often referred to as the cell’s energy factories.

Despite its importance, scientists had long struggled to understand how CoA reaches mitochondria. CoA rarely exists alone inside cells; instead, it attaches to other molecules, forming compounds known as CoA conjugates. This complexity made it difficult for researchers to track how the molecule moves within cells.

To solve this problem, the research team developed a new analytical approach using Mass Spectrometry. This advanced technology allowed scientists to identify and measure different CoA-related molecules with high precision. Using this method, they detected 33 types of CoA conjugates in whole cells and 23 types within mitochondria.

Further experiments revealed that CoA is not produced inside mitochondria. Instead, it is transported there through specialized cellular transport systems. When researchers removed the transport proteins responsible for this process, the levels of CoA inside mitochondria dropped significantly, confirming their role in delivering the molecule to these structures.

The discovery has important implications for human health. Disruptions in CoA transport have been linked to conditions such as Encephalomyopathy, which can cause developmental delays, seizures, and muscle weakness.

Understanding how CoA enters mitochondria may also help researchers explore new strategies for diagnosing and treating metabolic and neurodegenerative diseases.

REFERENCE: Ran Liu, Zihan Zhang, Aye K. Kyaw, Kariona A. Grabińska, Hardik Shah, Hongying Shen. Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. Nature Metabolism, 2025; 7 (9): 1871 DOI: 10.1038/s42255-025-01358-y