{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CALCOCO2 (also known as NDP52) functions as a selective autophagy receptor that plays a central role in the recognition and clearance of unwanted or harmful cellular cargo. It accomplishes this task by binding to ubiquitinated substrates and recruiting components of the autophagy machinery—most notably members of the LC3 family—to sites of damage or infection. In mitophagy, for example, CALCOCO2 is rapidly recruited to depolarized mitochondria (via PINK1‐dependent signals) to help couple ubiquitin tagging of damaged organelles with the assembly of autophagosomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the realm of host defense, CALCOCO2 is similarly critical: it is recruited—often in conjunction with cytosolic danger sensors such as galectin‐8 and kinases like TBK1—to ubiquitinated intracellular bacteria, thereby initiating antibacterial xenophagy and limiting pathogen proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, CALCOCO2 has been implicated in the regulation of other homeostatic processes; for instance, it contributes to the control of microRNA pathway components by mediating autophagic degradation of unbound DICER and AGO2, thus influencing miRNA loading and activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additionally, by forming defined complexes together with proteins such as FIP200 and SINTBAD/NAP1, CALCOCO2 helps coordinate the focal recruitment of upstream autophagy regulators to diverse cargo"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and it also participates in a negative feedback loop that curbs type I interferon signaling by targeting key signaling adaptors for autophagic degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Lazarou, Danielle A Sliter, Lesley A Kane, et al. 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