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Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation

Authors
  • Li, Tianxia1,
  • Liu, Jingnan
  • Guo, Gongbo1
  • Ning, Bo1, 2
  • Li, Xueping1, 2
  • Zhu, Guangjing1
  • Yang, Dejun1
  • Moran, Timothy H.1
  • Smith, Wanli W.1
  • 1 (T.H.M.)
  • 2 Institute of Obesity and Metabolic Diseases, School of Clinical Medicine, Xi’an Medical Collage, Xi’an 71000, China
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Jun 18, 2020
Volume
21
Issue
12
Identifiers
DOI: 10.3390/ijms21124352
PMID: 32570982
PMCID: PMC7352261
Source
PubMed Central
Keywords
License
Green

Abstract

A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemical approaches to investigate the cellular functions of synphilin-1 on the AMP-activated protein kinase (AMPK) signaling pathway, which may affect energy balance. Overexpression of synphilin-1 increased AMPK phosphorylation (activation). Moreover, synphilin-1 interacted with AMPK by co-immunoprecipitation and GST (glutathione S-transferase) pull-down assays. Knockdown of synphilin-1 reduced AMPK phosphorylation. Overexpression of synphilin-1 also altered AMPK downstream signaling, i.e., a decrease in acetyl CoA carboxylase (ACC) phosphorylation, and an increase in p70S6K phosphorylation. Treatment of compound C (an AMPK inhibitor) reduced synphilin-1 binding with AMPK. In addition, compound C diminished synphilin-1-induced AMPK phosphorylation, and the increase in cellular ATP (adenosine triphosphate) levels. Our results demonstrated that synphilin-1 couples with AMPK, and they exert mutual effects on each other to regulate cellular energy status. These findings not only identify novel cellular actions of synphilin-1, but also provide new insights into the roles of synphilin-1 in regulating energy currency, ATP.

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