[9a-S302-1~9] Cellular control by external stimulations: From stimulation transfer to expression of regulatory effects

11:25 AM - 11:55 AM JST(2:25 AM - 2:55 AM UTC)

[9a-S302-7] Control of excessive mitochondria fission under oxidative stress: development of inhibitors and multimodal imaging system

〇Soichi Wakatsuki^1,2, Suman Pokhrel¹, Gwangbeom Heo¹, Irimpan Mathews², Shun Yokoi^1,3, Tsutomu Matsui², Ayori Mitsutake³, Dara Dowlatshahi^1,2, Rose Knight^1,2, Jacob Summers^1,2, Abdullah Kepceoglu^1,2, Samsuzzoha Mondal^1,2, Adam Bowman⁴, Mark Kasevich¹, Daria Mockly-Rosen¹ (1.Stanford Univ., 2.SLAC, 3.Meiji Univ., 4.Salk Inst.)

Keywords:

Mitochondria fission,Inhibitors,Multimodal imaging method

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.