The regulation mechanisms of peroxisomal protein import and homeostasis.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Tamura Shigehiko 九州大学, 基幹教育院, 教授 (90236753)
• Co-Investigator(Kenkyū-buntansha): 藤木 幸夫 株式会社レオロジー機能食品研究所, 未登録, 九州大学名誉教授、顧問研究員、九州大学-レオロジー機能食品研究所 共同研究代表 (70261237)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ペルオキシソーム / リン酸化 / 酸化ストレス応答 / 細胞周期

Outline of Final Research Achievements

One central component of peroxisomal matrix protein import machinery is Pex14p, a peroxisomal membrane protein involved in the docking of Pex5p, the receptor for peroxisome targeting signal type 1. Studies in several yeast species have shown that Pex14p is phosphorylated in vivo, whereas no function has been assigned to Pex14p phosphorylation in yeast and mammalian cells. We investigated peroxisomal protein import and its dynamics in mitotic mammalian cells. In mitotically arrested cells, Pex14p is phosphorylated at Ser232, resulting in a lower import efficiency of catalase. Conformational change induced by the mitotic phosphorylation of Pex14p suppresses topological change of its N-terminal part, thereby giving rise to the retardation of Pex5p export in mitotic cells. Mitotic phosphorylation of Pex14p and consequent suppression of catalase import are a mechanism of protecting DNA upon nuclear envelope breakdown at mitosis.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、細胞内の環境変化に応答したペルオキシソーム機能の制御メカニズム解明に向けた手がかりを得ることができ、さらには細胞のストレス毒性に対するペルオキシソームの抗ストレス機能の解明に繋がるだけでなく、活性酸素種が関与する病気や老化の進行等に対する今後の治療法開発や創薬研究への展開が大きく期待される。