Excess Ceramide and Disrupted Iron Metabolism in Neuronal Mitochondria Found to Be the Cause of MEPAN Syndrome

A study published on August 31, 2023 in Nature Metabolism has revealed the pathogenic mechanism underlying a rare pediatric neurodegenerative disorder known as mitochondrial enoyl reductase protein-associated neurodegeneration (MEPAN) syndrome. The study was led by Dr. Hugo J. Bellen, DVM, PhD, Distinguished Service Professor at Baylor College of Medicine, and Chair of Neurogenetics at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital (Duncan NRI), and Dr. Debdeep Dutta, a postdoctoral fellow in the Bellen lab. The Duncan NRI team found that in patients and animal models of this disorder, a large number of neurons die due to excessive accumulation of ceramide and defective iron metabolism, which results from disruptions in mitochondrial fatty acid synthesis. It is the first study to provide a mechanistic link between disruptions in mitochondrial fatty acid synthesis, iron and ceramide metabolism, and neurodegeneration. The open-access article is titled “A Defect in Mitochondrial Fatty Acid Synthesis Impairs Iron Metabolism and Causes Elevated Ceramide Levels.”

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