Analysis of a new intracellular proteolysis mechanism GOMED using Golgi membrane

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Arakawa Satoko 東京医科歯科大学, 統合研究機構, 教授 (90415159)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: GOMED / Golgi / neurodegeneration / ceruloplasmin / Autophagy / Cell Death

Outline of Final Research Achievements

GOMED is an Atg5/Atg7-independent type of autophagy that contributes to various physiological events.　In this study, we identified Wipi3 as a molecule essential for GOMED.　Wipi3 altered the distribution from the cytoplasm to the trans-Golgi membrane and was indispensable for the formation of isolated membranes.
Next, we analyzed neuron-specific Wipi3-deficient mice, which showed behavioral abnormalities. In the cerebellum, neuronal cells exhibited an accumulation of iron and ceruloplasmin and these caused the neuronal degeneration.　　Based on these findings, GOMED appears to play a critical role in neuronal cell maintenance.

Free Research Field

組微細構造生物学

Academic Significance and Societal Importance of the Research Achievements

通常のATg5/Atg7を用いるオートファジーではER膜から隔離膜が形成されるが、GOMEDはそれとは異なり、ゴルジ体のトランス膜を用いるなど、隔離膜の由来が異なり、また通常のオートファジーとは異なる分子メカニズムを用いていることが判明した。さらに生体内においても、通常のオートファジーとは異なる生理的機能を持つこと、特に、脳の神経細胞において、鉄蓄積を防いでいるということを明らかとした。