Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases

In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular organelles, peroxisomes support key metabolic platforms for the oxidation of various fatty acids and regulate redox conditions. In addition, peroxisomes contribute to the biosynthesis of essential lipid molecules, such as bile acid, cholesterol, docosahexaenoic acid, and plasmalogen. Therefore, the quality control mechanisms that regulate peroxisome biogenesis and degradation are important for cellular homeostasis. Current evidence indicates that peroxisomal function is often reduced or dysregulated in various human disease conditions, such as neurodegenerative diseases. Here, we review the recent progress that has been made toward understanding the quality control systems that regulate peroxisomes and their pathological implications. Neurodegenerative diseases: The role of peroxisome organelles Systematic studies of cellular organelles called peroxisomes are needed to determine their influence on the progression of neurodegenerative diseases. Peroxisomes play vital roles in biological processes including the metabolism of lipids and reactive oxygen species, and the synthesis of key molecules, including bile acid and cholesterol. Disruption to peroxisome activity has been linked to metabolic disorders, cancers and neurodegenerative conditions. Dong-Hyung Cho at Kyungpook National University in Daegu, South Korea, and coworkers reviewed current understanding of peroxisome regulation, with a particular focus on brain disorders. The quantity and activity of peroxisomes alter according to environmental and stress cues. The brain is lipid-rich, and even small changes in fatty acid composition may influence neuronal function. Changes in fatty acid metabolism are found in early stage Alzheimer’s and Parkinson’s diseases, but whether peroxisome disruption is responsible requires clarification.