RETREG3/FAM134C phosphorylation by CSNK2 regulates reticulophagy during starvation

Abstract

Starvation is the most potent physiological inducer of autophagy, the catabolic process which degrades unessential cytosolic components to sustain cellular homeostasis and survival. During starvation, the mechanisms of autophagy activation have been extensively investigated; however, less is known about how substrate selection occurs. In this punctum, we summarize our recent findings that delineate a novel signaling pathway that promotes selective autophagic removal of parts of the endoplasmic reticulum (reticulophagy) during starvation. We demonstrate that the inhibition of MTORC1 results in the activation of the reticulophagy receptor RETREG3/FAM134C by preventing its phosphorylation by CSNK2/CK2. In vivo, RETREG3 depletion impairs MTORC1-dependent regulation of lipid metabolism in liver. Last, we describe a novel approach to study selective autophagy in vivo, which might be exploited to identify novel physiological roles of autophagy.

Keywords: CSNK2; MTORC1; RETREG3; endoplasmic reticulum; reticulophagy.

Figure 1.

Proposed model of reticulophagy regulation by CSNK2. CSNK2 phosphorylates the reticulophagy receptors RETREG3 and TEX264 at the indicated residues (red) promoting or inhibiting, respectively the binding of the LIR domain (green) with LC3.