
단백질 응집체 성숙화 과정에서 스핑고지질 대사 경로가 핵심적인 역할을 하며, 이를 통해 세포는 병원성 단백질 응집체의 독성을 해독할 수 있다.


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Due to proteostasis stress induced by aging or disease, misfolded proteins can form toxic intermediate species of aggregates and eventually mature into less toxic inclusion bodies (IBs). Here, using a yeast imaging-based screen, we identified 84 potential synphilin-1 (SY1) IB regulators and isolated the conserved sphingolipid metabolic components in the most enriched groups. Furthermore, we show that, in both yeast cells and mammalian cells, SY1 IBs are associated with mitochondria. Pharmacological inhibition of the sphingolipid metabolism pathway or knockout of its key genes results in a delayed IB maturation and increased SY1 cytotoxicity. We postulate that SY1 IB matures by association with the mitochondrion membrane, and that sphingolipids stimulate the maturation via their membrane-modulating function and thereby protecting cells from SY1 cytotoxicity. Our findings identify a conserved cellular component essential for IB maturation and suggest a mechanism by which cells may detoxify the pathogenic protein aggregates through forming mitochondrion-associated IBs.

### Competing Interest Statement

The authors have declared no competing interest.

Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids

단백질-응집체-성숙화와-해독화에-있어-스핑고지질의-역할


단백질 응집체 성숙화와 해독화에 있어 스핑고지질의 역할
