Lipid droplets trigger aberrant α-synuclein phase separation and mitochondrial dysfunction

Lipid droplets promote spontaneous liquid-liquid phase separation of wild-type and E46K mutant α-synuclein. These condensates impair lipid droplet turnover and disrupt mitochondrial function, suggesting a mechanism for neurodegeneration in Parkinson’s disease.

• In vitro study (sample size not reported) demonstrates that lipid droplets drive phase separation of α-synuclein.
• αSyn condensates sequester lipid droplets, impairing turnover, and cause mitochondrial membrane potential reduction and increased mitophagy.
• Limitation: in vitro findings; in vivo validation needed to confirm relevance to Parkinson’s disease neurodegeneration.

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