YIPF3 and YIPF4 regulate autophagic turnover of the Golgi apparatus

EMBO J. 2024 Jul;43(14):2954-2978. doi: 10.1038/s44318-024-00131-3. Epub 2024 May 31.

Abstract

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.

Keywords: Autophagy Receptor; Golgi Turnover; Golgiphagy; Organelle Degradation; Selective Autophagy.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy*
  • Golgi Apparatus* / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Proteomics / methods

Substances

  • Microtubule-Associated Proteins
  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • MAP1LC3B protein, human
  • GABARAPL1 protein, human
  • Apoptosis Regulatory Proteins
  • GABARAP protein, human
  • Membrane Transport Proteins