講演情報
[9a-S302-7]酸化ストレス化における過剰なミトコンドリア分裂の制御：阻害剤開発とマルチモーダルイメージング法の開発
〇若槻 壮市1,2、ポクレル スマン1、ヘオ グワンボム1、マシューズ イリンパン2、横井 俊1,3、松井 勉2、光武 亜代理3、ダウラッチャハイ ダラ1,2、ナイト ロウズ1,2、サマーズ ジエイコブ1,2、ケプセオグル アブダラ1,2、モンダル サムスゾハ1,2、ボウマン アダム4、カセヴィッチ マーク1、モクリーローゼン ダリア1 (1.スタンフォード大学、2.SLAC、3.明治大理工、4.ソーク研究所)
キーワード：
ミトコンドリア分裂、阻害剤、マルチモーダルイメージング法
Mitochondria are dynamic organelles, and fusion and fission maintain mitochondrial size, morphology and function. Fis1-mediated mitochondrial localization of Drp1 and excessive mitochondrial fission occur in human pathologies associated with oxidative stress. However, it is not known how Fis1 detects oxidative stress and what structural changes in Fis1 enable mitochondrial recruitment of Drp1. We have found that Fis1 senses the oxidative stress and exposes its only cysteine, Cys41 to dimerize and recruit Drp1 for fission, and discovered a small molecule, SP11, that binds only to activated Fis1 by engaging Cys41. SP11 preserves mitochondrial integrity and function in cells during oxidative stress and thus may serve as a candidate molecule for the development of treatment for diseases with underlying Fis1-mediated mitochondrial fragmentation and dysfunction. As a next step, we will report our project to develop multimodal imaging systems including electro-optical fluorescence lifetime imaging microscopy (EO-FLIM) and cryo-ET, in order to visualize cells, mitochondria and other organelles in response to external stress and drugs.