Lipid-fuelled synaptic plasticity: integrating membrane turnover, β-oxidation, and protein lipidation.

Lipid flux involving saturated free fatty acids links membrane remodelling, energy production, and protein turnover at synapses, with DDHD2 as a key regulator.

• Why it matters: Understanding how these processes are integrated is crucial for revealing mechanisms underlying synaptic plasticity and neurodegenerative diseases, yet remains unclear.
• What they did: The study proposes activity-dependent lipid flux as a central mechanism, highlighting pathways where saturated free fatty acids are activated to acyl-CoA, then directed to mitochondrial β-oxidation and protein lipidation, with DDHD2 identified as a mechanistic entry point.
• The result: This work suggests that lipid mobilization and fatty acid metabolism are interconnected at synapses, providing insights into their roles in membrane dynamics and energy supply, which may be altered in neurodegenerative conditions.