Mitochondria and Lipids in Cellular Signaling of the Brain: from Physiology to Neurodegeneration

The brain is one of the most lipid-rich organs, reflecting the critical role of lipid metabolism in neuronal and glial cell function. While mitochondria are central to energy metabolism, calcium signaling, and cell death, they do not utilize lipid oxidation for energy but rely on lipids for membrane integrity and intracellular communication. Here we review the interactions between lipids and mitochondria in intracellular signaling within brain cells, examining their roles in normal physiology and the mechanisms underlying major neurodegenerative diseases. Alterations in lipid homeostasis and mitochondrial metabolism are implicated in neurodegeneration, highlighting the importance of lipid-mediated mitochondrial signaling pathways. Understanding these interactions provides insights into cellular dysfunction in neurodegenerative disorders and may inform future therapeutic strategies targeting lipid and mitochondrial pathways.