FBS Colloquia No.311Laboratory of Intracellular Membrane Dynamics
| Seminar or Lecture |
1. Mechanism of autophagy initiation during non-selective/selective autophagy. Keisuke Tabata [Assistant professor, Laboratory of intracellular membrane dynamics (Yoshimori Lab)] 2. Elucidation of the mechanisms regulating lifespan and autophagy Tatsuya Shioda [FBS PhD student, D4, Laboratory of intracellular membrane dynamics (Yoshimori Lab)] |
|---|---|
| Date and Time | 20 Oct. 2022 (Thu), 12:15～13:00 |
| Place | Online (Zoom) | An email will be sent with the meeting URL, ID, and password to all FBS members. |
| Language | Japanese |
| Contact |
Maho Hamasaki (Associate Professor) |
1. Mechanism of autophagy initiation during non-selective/selective autophagy.
Macroautophagy (so called autophagy) is a highly conserved intracellular degradation system to maintain cellular homeostasis by degrading cellular conponents such as misfolded proteins, nonfunctional organelles, pathogens and cytosol. Nonselective autophagy randomly engulfs a portion of cellular components into double membrane vesicle called autophagosome and then delivers them into lysosome for degradation. Selective autophagy, however, specifically recognizes and degrades cargos. In FBS seminar, two topics will be introduced. (1) In non-selective autophagy, ULK1 complex is essential to initiate autophagy and known to be recruited to autophagosome formation site. However, molecular mechanism of ULK1 recruitment has been unclear. Here, I will talk about an enzyme regulating ULK1 membrane anchoring. (2) Although we previously reported damaged lysosomes are degraded by selective autophagy called lysophagy, we have not known how damaged lysosomes are selectively recognized. In this seminar, I would like to show that CUL4A E3 ligase complex ubiquitinates lysosomal protein, LAMP2. This protein modification is critical for degradation of damaged lysosomes.
2. Elucidation of the mechanisms regulating lifespan and autophagy
During last 20 decades, the evolutionally conserved molecular mechanisms which are related to animal aging or lifespan have been identified from several model organisms including yeast, worms, flies and mice. These mechanisms, so called longevity pathway, for instance, include reduced Insulin/IGF-1 signaling, dietary restriction, reduced TOR signaling, germline removal and reduced mitochondrial respiration. Extensive efforts to identify the downstream mechanism in each longevity pathway reveals that a cytoplasmic degradation system known as autophagy is one of the convergent mechanisms of all longevity pathways. However, how autophagy is regulated in these longevity pathways remain largely unclear. We have previously discovered a key role for transcription factor MML-1/MondoA and its partner MXL-2/Max-like in these multiple longevity pathways (Nakamura et al., Nat Commun, 2016). MML-1/MXL-2 complex is activated in these longevity pathways and required for autophagic activation and lifespan extension. However, critical tissues where MML-1/MXL-2 regulates autophagy and longevity remain elusive. Using a tissue-specific RNAi system in C. elegans, we found that knockdown of MML-1/MXL-2 in specific tissue abrogated longevity. We also found genetic evidence showing inter-tissue regulation of autophagy and longevity by MML-1/MXl-2. In this seminar, I would like to introduce the tissue-specific role of MML-1/MXL-2 in lifespan extension.
