AI Article Synopsis
- Brown adipocytes are crucial for regulating body temperature and metabolism, adapting their activity based on nutrient availability, and autophagy plays a key role in this process.
- The study investigates the amino acid transporter PAT2/SLC36A2 in brown adipocytes, examining its effects on cellular functions like differentiation and lysosomal activity when amino acids are scarce.
- Findings reveal that PAT2 helps move to lysosomes in low nutrient conditions, affecting lysosomal acidification and its assembly, highlighting its role as a sensor of amino acids in brown adipocytes.
Article Abstract
Objective: Brown adipocytes play a key role in maintaining body temperature as well as glucose and lipid homeostasis. However, brown adipocytes need to adapt their thermogenic activity and substrate utilization to changes in nutrient availability. Amongst the multiple factors influencing brown adipocyte activity, autophagy is an important regulatory element of thermogenic capacity and activity. Nevertheless, a specific sensing mechanism of extracellular amino acid availability linking autophagy to nutrient availability in brown adipocytes is unknown.
Methods: To characterize the role of the amino acid transporter PAT2/SLC36A2 in brown adipocytes, loss or gain of function of PAT2 were studied with respect to differentiation, subcellular localization, lysosomal activity and autophagy. Activity of vATPase was evaluated by quenching of EGFP fused to LC3 or FITC-dextran loaded lysosomes in brown adipocytes upon amino acid starvation, whereas the effect of PAT2 on assembly of the vATPase was investigated by Native-PAGE.
Results: We show that PAT2 translocates from the plasma membrane to the lysosome in response to amino acid withdrawal. Loss or overexpression of PAT2 impair lysosomal acidification and starvation-induced S6K re-phosphorylation, as PAT2 facilitates the assembly of the lysosomal vATPase, by recruitment of the cytoplasmic V1 subunit to the lysosome.
Conclusions: PAT2 is an important sensor of extracellular amino acids and regulator of lysosomal acidification in brown adipocytes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114668 | PMC |
| http://dx.doi.org/10.1016/j.molmet.2022.101508 | DOI Listing |
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