Lifespan extension by peroxidase/dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14574
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Nagoya University
• Principal Investigator: MORI Ikue 名古屋大学, 理学研究科, 教授 (90219999)
• Co-Investigator(Renkei-kenkyūsha): NAKANO Shunji 名古屋大学, 大学院理学研究科, 助教 (60608529) ; TSUKADA Yuki 名古屋大学, 大学院理学研究科, 助教 (80580000)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 老化 / 活性酸素 / 遺伝学 / 線虫

Outline of Final Research Achievements

Reactive oxygen species (ROS) are recognized as important signal molecules regulating various biological processes. Low levels of ROS released from mitochondria extend lifespan. We identified a novel mechanism of ROS-mediated lifespan extension by generating fine-tuned ROS level at the plasma membrane through a peroxidase/dual oxidase system in Caenorhabditis elegans. A redox co-factor, pyrroloquinoline quinone (PQQ), activates dual oxidase (DUOX)/BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase/MLT-7 to generate the appropriate levels of ROS. The ROS signal appeared to be mediated by the oxidative stress transcriptional factors SKN-1/Nrf2 and JUN-1. We propose that low levels of ROS, fine-tuned by the peroxidase/dual oxidase system at the plasma membrane, act as second messengers, to extend lifespan by the effect of hormesis.

Free Research Field

神経科学