The degradation of organelles by autophagy is essential for cellular homeostasis. The Golgi apparatus has recently been demonstrated to be degraded by autophagy, but little is known about how the Golgi is recognized by the forming autophagosome. Using quantitative proteomic analysis and two novel Golgiphagy reporter systems, we found that the five-pass transmembrane Golgi-resident proteins YIPF3 and YIPF4 constitute a Golgiphagy receptor. The interaction of this complex with LC3B, GABARAP, and GABARAPL1 is dependent on a LIR motif within YIPF3 and putative phosphorylation sites immediately upstream; the stability of the complex is governed by YIPF4. Expression of a YIPF3 protein containing a mutated LIR motif caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy. The reporter assays reported here may be readily adapted to different experimental contexts to help deepen our understanding of Golgiphagy.
Synopsis: The selective autophagy of damaged organelles is a key process ensuring cellular homeostasis. In this study, a trans-membrane Golgiphagy receptor, comprising YIPF3 and YIPF4, is identified and its mechanism described.Development of two novel reporters enables quantitative evaluation of Golgiphagy.The novel Golgiphagy reporters reveal that the YIPF3-YIPF4 complex functions as a Golgiphagy receptor.The YIPF3-YIPF4 complex interacts with specific ATG8s via the LIR motif in YIPF3, whose stability is dependent on YIPF4.The interaction of YIPF3 with ATG8s is dependent on putative phosphorylation sites immediately upstream of LIR motif, which is similar to the major ER-phagy receptor TEX264.
Two Golgi-resident transmembrane proteins interact to form a Golgiphagy receptor.