bims-lypmec Biomed News
on Lysosomal positioning and metabolism in cardiomyocytes
Issue of 2022‒09‒18
two papers selected by
Satoru Kobayashi
New York Institute of Technology
  1. Conjugation of the ubiquitin family proteins to phospholipids.
  2. Identification of CUL4A-DDB1-WDFY1 as an E3 ubiquitin ligase complex involved in initiation of lysophagy.
  1. Autophagy. 2022 Sep 12.
    Conjugation of the ubiquitin family proteins to phospholipids.
    Jun-Ichi Sakamaki, Noboru Mizushima.
      Conjugation of Atg8-family proteins to phosphatidylethanolamine (PE) is important for autophagosome formation. PE conjugation has been thought to be specific to Atg8 among the ubiquitin-family proteins. However, this dogma has not been experimentally verified. Our recent study revealed that ubiquitin is also conjugated to PE on endosomes and the vacuole (or lysosomes). Other ubiquitin-like proteins, such as NEDD8 and ISG15, also covalently bind to phospholipids. We propose that conjugation to phospholipids could be a common feature of the ubiquitin family.
    Keywords:  Atg8; Doa4; Tul1; endosome; lysosome; phosphatidylethanolamine; phospholipids; ubiquitin; ubiquitin-like proteins; vacuole
    DOI:  https://doi.org/10.1080/15548627.2022.2123637
  2. Cell Rep. 2022 Sep 13. pii: S2211-1247(22)01177-9. [Epub ahead of print]40(11): 111349
    Identification of CUL4A-DDB1-WDFY1 as an E3 ubiquitin ligase complex involved in initiation of lysophagy.
    Hirofumi Teranishi, Keisuke Tabata, Marika Saeki, Tetsuo Umemoto, Tomohisa Hatta, Takanobu Otomo, Kentaro Yamamoto, Toru Natsume, Tamotsu Yoshimori, Maho Hamasaki.
      Macroautophagy is a bulk degradation system in which double membrane-bound structures called autophagosomes 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 machinery. 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.
    Keywords:  CP: Molecular biology; CUL4A; LAMP2; autophagy; lysophagy; lysosomal membrane damage; ubiquitination
    DOI:  https://doi.org/10.1016/j.celrep.2022.111349
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