PAT2 regulates autophagy through vATPase assembly and lysosomal acidification in brown adipocytes

Abstract

2 Brown adipose tissue (BAT) plays a key role in maintaining body temperature as well as glucose and lipid homeostasis by its ability to dissipate energy through mitochondrial uncoupling. To facilitate these tasks BAT needs to adopt its thermogenic activity and substrate utilization to changes in nutrient availability, regulated by a complex network of neuronal, endocrine and nutritional inputs. Amongst this multitude of factors influencing BAT activity changes in the autophagic response of brown adipocytes are an important regulator of its thermogenic capacity and activity. Increasing evidence supports an important role of amino acid transporters in mTORC1 activation and the regulation of autophagy. However, a specific role of amino acid transporters in BAT regulating its function has not been described. Here we show that the brown adipocyte specific proton coupled amino acid transporter PAT2 rapidly translocates from the plasma membrane to the lysosome in response to amino acid withdrawal, where it facilitates the assembly of the lysosomal vATPase. Loss or overexpression of PAT2 therefore impair lysosomal acidification, autophagolysosome formation and starvation induced mTORC1 activation.

Identification and characterization of adipose surface epitopes

“…Low mRNA expression of PAT2 can be found outside beige/brown fat, but how that translates to protein levels remains unknown. Furthermore, we recently showed that the surface location of PAT2 is highly dependent on extracellular amino acid concentrations, and could strongly fluctuate in vivo [ 298 ].…”