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Lipid Droplet-Associated Hydrolase Promotes Lipid Droplet Fusion and Enhances ATGL Degradation and Triglyceride Accumulation.
Goo, Young-Hwa; Son, Se-Hee; Paul, Antoni.
Afiliação
  • Goo YH; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA. gooy@mail.amc.edu.
  • Son SH; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA.
  • Paul A; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA. paula@mail.amc.edu.
Sci Rep ; 7(1): 2743, 2017 06 02.
Article em En | MEDLINE | ID: mdl-28578400
Lipid droplet (LD)-associated hydrolase (LDAH) is a newly identified LD protein abundantly expressed in tissues that predominantly store triacylglycerol (TAG). However, how LDAH regulates TAG metabolism remains unknown. We found that upon oleic acid loading LDAH translocalizes from the ER to newly formed LDs, and induces LD coalescence in a tubulin-dependent manner. LDAH overexpression and downregulation in HEK293 cells increase and decrease, respectively, TAG levels. Pulse and chase experiments show that LDAH enhances TAG biogenesis, but also decreases TAG turnover and fatty acid release from cells. Mutations in predicted catalytic and acyltransferase motifs do not influence TAG levels, suggesting that the effect is independent of LDAH's enzymatic activity. However, a LDAH alternative-splicing variant missing 90 amino acids at C-terminus does not promote LD fusion or TAG accumulation, while it still localizes to LDs. Interestingly, LDAH enhances polyubiquitination and proteasomal degradation of adipose triglyceride lipase (ATGL), a rate limiting enzyme of TAG hydrolysis. Co-expression of ATGL reverses the changes in LD phenotype induced by LDAH, and both proteins counterbalance their effects on TAG stores. Together, these studies support that under conditions of TAG storage in LDs LDAH plays a primarily lipogenic role, inducing LD growth and enhancing degradation of ATGL.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Metabolismo dos Lipídeos / Gotículas Lipídicas / Lipase Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triglicerídeos / Metabolismo dos Lipídeos / Gotículas Lipídicas / Lipase Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article