Multiple functions of CALCOCO family proteins in selective autophagy

Abstract Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors. CALCOCO family proteins are the newly found selective autophagy receptors, which include calcium binding and coiled‐coil domain 1 (CALCOCO1), calcium binding and coiled‐coil domain 2/nuclear domain 10 protein 52 (CALCOCO2/NDP52), and calcium binding and coiled‐coil domain 3/Tax1‐binding protein 1 (CALCOCO3/TAX1BP1). Specifically, CALCOCO1 can be recruited to endoplasmic reticulum (ER) and Golgi to mediate selective ER‐phagy and Golgiphagy. CALCOCO2 and CALCOCO3, which are two essential cargo receptors, can mediate mitophagy and xenophagy through interacting with autophagy‐related‐8/microtubule‐associated protein 1 light chain 3 (ATG8/LC3) on the growing autophagosome, and binding ubiquitin for cargo recruitment. Considering the significance of these proteins in selective autophagy, we review the structures, distribution, posttranslational modifications, and phylogenetic analysis of CALCOCO family proteins and their roles in different selective autophagy.