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Updated: Sep 2, 2025
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
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DHHC17 Is a New Regulator of AMPK Signaling
1Department of Medicine, Tufts Medical Centergrid.67033.31, Boston, Massachusetts, USA.
Molecular and Cellular Biology
|August 1, 2022
Summary
AMP-activated protein kinase alpha (AMPKα) palmitoylation is essential for its activation and membrane association. DHHC17 enzyme regulates this process, impacting hepatic metabolism and causing type 2 diabetes-like symptoms when impaired.
Area of Science:
- Cellular Biology
- Metabolic Regulation
- Biochemistry
Background:
- AMP-activated protein kinase (AMPK) regulates cellular energy.
- Protein lipidation, including palmitoylation, is key for membrane protein interactions.
- AMPKα subunit is known to be palmitoylated, but its regulation and function are not fully understood.
Purpose of the Study:
- To characterize AMPKα palmitoylation.
- To identify the enzyme responsible for AMPKα palmitoylation.
- To investigate the role of AMPKα palmitoylation and its regulator in hepatic metabolism and diabetes.
Main Methods:
- Site-directed mutagenesis to identify palmitoylation sites on AMPKα.
- Biochemical assays to confirm palmitoylation and enzyme activity.
- Generation and analysis of DHHC17 liver-specific knockout mice.
Main Results:
- AMPKα is palmitoylated at Cys209 and Cys543, which is critical for its activation and membrane localization.
- DHHC17 was identified as the palmitoyltransferase for AMPKα, modulating its membrane association and activation.
- DHHC17 deficiency in mouse liver impaired AMPK activation, hepatic autophagy, and led to a type 2 diabetes-like syndrome.
Conclusions:
- AMPKα palmitoylation is a crucial regulatory mechanism for AMPK activation and cellular function.
- DHHC17 is a novel regulator of AMPK signaling and hepatic metabolism.
- Dysregulation of DHHC17-mediated AMPK palmitoylation contributes to metabolic disorders like type 2 diabetes.
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