Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4

Autophagy is an evolutionarily conserved catabolic mechanism that targets intracellular molecules and damaged organelles to lysosomes. Autophagy is achieved by a series of membrane trafficking events, but their regulatory mechanisms are poorly understood. Here, we report small GTPase Rab12 as a new type of autophagic regulator that controls the degradation of an amino‐acid transporter. Knockdown of Rab12 results in inhibition of autophagy and in increased activity of mTORC1 (mammalian/mechanistic target of rapamycin complex 1), an upstream regulator of autophagy. We also found that Rab12 promotes constitutive degradation of PAT4 (proton‐coupled amino‐acid transporter 4), whose accumulation in Rab12‐knockdown cells modulates mTORC1 activity and autophagy. Our findings reveal a new mechanism of regulation of mTORC1 signalling and autophagy, that is, quality control of PAT4 by Rab12. This study identifies the small GTPase Rab12 as a new type of autophagic regulator that controls the degradation of the amino‐acid transporter PAT4. Knockdown of Rab12 inhibits autophagy and activates mTORC1, an upstream regulator of autophagy, presumably by increased amino acid uptake through PAT4.