Phospholipase Lpl1 links lipid droplet function with quality control protein degradation.
Mol Biol Cell
; 28(6): 716-725, 2017 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-28100635
ABSTRACT
Protein misfolding is toxic to cells and is believed to underlie many human diseases, including many neurodegenerative diseases. Accordingly, cells have developed stress responses to deal with misfolded proteins. The transcription factor Rpn4 mediates one such response and is best known for regulating the abundance of the proteasome, the complex multisubunit protease that destroys proteins. Here we identify Lpl1 as an unexpected target of the Rpn4 response. Lpl1 is a phospholipase and a component of the lipid droplet. Lpl1 has dual functions it is required for both efficient proteasome-mediated protein degradation and the dynamic regulation of lipid droplets. Lpl1 shows a synthetic genetic interaction with Hac1, the master regulator of a second proteotoxic stress response, the unfolded protein response (UPR). The UPR has long been known to regulate phospholipid metabolism, and Lpl1's relationship with Hac1 appears to reflect Hac1's role in stimulating phospholipid synthesis under stress. Thus two distinct proteotoxic stress responses control phospholipid metabolism. Furthermore, these results provide a direct link between the lipid droplet and proteasomal protein degradation and suggest that dynamic regulation of lipid droplets is a key aspect of some proteotoxic stress responses.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfolipasas
/
Factores de Transcripción
/
Proteínas de Saccharomyces cerevisiae
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Proteínas de Unión al ADN
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Respuesta de Proteína Desplegada
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Gotas Lipídicas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Biol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2017
Tipo del documento:
Article