Quality control mechanism by AAA-ATPase Msp1 on the outer mitochondrial membrane

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21471
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry; Cell biology
• Research Institution: Kyoto Sangyo University
• Principal Investigator: MATSUMOTO Shunsuke 京都産業大学, タンパク質動態研究所, 研究員 (70704295)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Msp1 / 品質管理 / ミトコンドリア / ミスターゲット / Cdc48 / Doa10 / コンタクトサイト

Outline of Final Research Achievements

This study aims to reveal the degradation pathway of mistargeted tail-anchored (TA) proteins on the outer mitochondrial membrane (OM). We identified protein factors involved in the degradation of the mistargeted TA proteins and analyzed roles of these factors by using yeast as a model system. We found that Msp1, an AAA-ATPase on the OM recruits the mistargeted TA proteins at contact site between endoplasmic reticulum (ER) and mitochondria, and promotes ubiquitination of the mistargeted TA proteins by Doa10, an ER-localized E3 ligase. Then, ubiquitinated mistargeted TA proteins on the OM were extracted by an another AAA-ATPase in cytosol, Cdc48 and were degraded by the proteasome.

Free Research Field

分子生物学・細胞生物学

Academic Significance and Societal Importance of the Research Achievements

近年，パーキンソン病を始めとする神経変性疾患や糖尿病，発がんや腫瘍の悪性化などの病態とミトコンドリア機能・品質管理の関連が明らかとなっている．本研究の成果は，ミトコンドリアの機能破綻や品質管理異常が原因となって引き起こされる難治性疾患の治療法開発の基盤を与える事も期待される．