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Wang, J. ; Onogi, Y. ; Krueger, M.* ; Oeckl, J.* ; Karlina, R. ; Singh, I. ; Hauck, S.M. ; Feederle, R. ; Li, Y.* ; Ussar, S.

PAT2 regulates vATPase assembly and lysosomal acidification in brown adipocytes.

Mol. Metab. 61:101508 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Brown Adipocytes ; Lysosomal Acidification ; Proton-coupled Amino Acid Transporter ; Transporter Translocation Across Membranes ; V-atpase Assembly
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 61, Heft: , Seiten: , Artikelnummer: 101508 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
CF Metabolomics & Proteomics (CF-MPC)
CF Monoclonal Antibodies (CF-MAB)
POF Topic(s) 30201 - Metabolic Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-502296-001
G-505700-001
A-631900-001
A-630700-001
DOI 10.1016/j.molmet.2022.101508
WOS ID WOS:000804540600001
Scopus ID 85129917367
PubMed ID 35513259
Erfassungsdatum 2022-09-14
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