Regulation of AMP-Activated Protein Kinase (AMPK) Subunit Expression at the Transcriptional Level by the Neutral Amino Acid Transporter SNAT2

Kun Tae; Sang Woo Cho; Ho Yeon Lee; Hyo Sun Cha; Cheol Yong Choi*

Kun Tae, Sang Woo Cho, Ho Yeon Lee, Hyo Sun Cha and Cheol Yong Choi*

Volume4-Issue9
Dates: Received: 2023-09-13 | Accepted: 2023-09-17 | Published: 2023-09-18
Pages: 1314-1322

Abstract

AMP-Activated Protein Kinase (AMPK) is a key enzyme that maintains cellular energy homeostasis. AMPK promotes catabolic pathways and inhibits anabolic pathways under low-energy conditions, such as glucose deprivation. SLC38A2/SNAT2 is an amino acid transporter that imports a wide range of neutral amino acids, including glutamine and alanine. The expression of SNAT2 is down regulated in patients with metabolic diseases such as obesity, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Here, we demonstrate that SNAT2 is required for LKB1-mediated activation of AMPK. Depletion of SNAT2 results in diminished activation of AMPK under conditions of glucose or serum starvation, while the induction of SNAT2 expression augments AMPK activation. SNAT2 overexpression-mediated induction of AMPK activation is abrogated by LKB1 depletion but not by CaMKK2 or TAK1 depletion. Interestingly, the mRNA levels of AMPKβ2 are comparably reduced by SNAT2 depletion, indicating regulation of AMPKβ2 at the transcriptional level. AMPKβ1 mRNA levels are also reduced to a lesser extent. Consistently, SNAT2 depletion leads to a marked reduction in AMPK-mediated autophagy induction, as evidenced by reduced conversion to LC3 II and LC3 puncta formation under nutrient-deprived conditions. Given that AMPK activation plays a pivotal role in nutrient sensing and the subsequent cellular response to low-energy levels and various stress conditions, we provide another level of regulatory mechanism for AMPK-mediated cellular energy homeostasis.

FullText HTML FullText PDF DOI: 10.37871/jbres1800

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Tae K, Cho SW, Lee HY, Cha HS, Choi CY. Regulation of AMP-Activated Protein Kinase (AMPK) Subunit Expression at the Transcriptional Level by the Neutral Amino Acid Transporter SNAT2. J Biomed Res Environ Sci. 2023 Sep 18; 4(9): 1314-1322. doi: 10.37871/jbres1800, Article ID: JBRES1800, Available at: https://www.jelsciences.com/articles/jbres1800.pdf

Subject area(s)

Cellular Biology

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