Identification of CUL4A- DDB1-WDFY1 as the E3 ubiquitin ligase complex to initiate lysophagy
Journal | Cell Reports 40, 111349 (2022) |
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Title | Identification of CUL4A- DDB1-WDFY1 as the E3 ubiquitin ligase complex to initiate lysophagy |
Laboratory | Laboratory of Intracellular Membrane Dynamics |
Abstract
Macroautophagy is a bulk degradation system in which double membrane-bound structures called autophago- somes to deliver cytosolic materials to lysosomes. Autophagy promotes cellular homeostasis by selectively recognizing and sequestering specific targets, such as damaged organelles, protein aggregates, and invading bacteria, termed selective autophagy. We previously reported a type of selective autophagy, lysophagy, which helps clear damaged lysosomes. Damaged lysosomes become ubiquitinated and recruit autophagic machin- ery. Proteomic studies using transfection reagent-coated beads and further evaluations reveal that a CUL4A- DDB1-WDFY1 E3 ubiquitin ligase complex is essential to initiate lysophagy and clear damaged lysosomes. Moreover, we show that LAMP2 is ubiquitinated by the CUL4A E3 ligase complex as a substrate on damaged lysosomes. These results reveal how cells selectively tag damaged lysosomes to initiate autophagy for the clearance of lysosomes.
Authors | Hirofumi Teranishi (1, 6), Keisuke Tabata (2, 3), Marika Saeki (2), Tetsuo Umemoto (2), Tomohisa Hatta (4), Takanobu Otomo (3), Kentaro Yamamoto (2), Toru Natsume (4), Tamotsu Yoshimori (2, 3, 5), Maho Hamasaki (2, 3)
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PubMed | 36103833 |