Identification of the YIPF3-YIPF4 heterodimer as a novel Golgiphagy receptor

Abstract

ABSTRACT Golgiphagy is a selective form of macroautophagy, characterized by the targeted degradation of Golgi compartments through specific receptors. In two recent studies, the YIPF3-YIPF4 heterodimer has been independently identified as the first Golgiphagy receptor within mammalian cells. This heterodimeric complex exhibits a direct affinity for mammalian Atg8-family proteins (ATG8s), thereby facilitating the expansion of phagophores in proximity to Golgi regions. Notably, the interaction between YIPF3-YIPF4 heterodimers and ATG8s undergoes regulatory modulation through phosphorylation. Furthermore, cells lacking either YIPF3 or YIPF4 display defects in Golgiphagy. To elucidate the physiological relevance of these proteins, the necessity of YIPF3-YIPF4 in orchestrating Golgi proteome remodeling was substantiated through experimentation in an in vitro neuronal differentiation model.Abbreviation: ATG: autophagy related; ATG8s: mammalian Atg8-family proteins; LIR, LC3-interacting region