日本理化研究所Atsushi Miyawaki、武田制药有限公司Yoshiyuki Tsujihata等研究人员合作开发了新型线粒体自噬探针，可用于神经退行性疾病的研究。该研究于2020年5月20日在线发表于《细胞》。

Title: Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration

Author: Hiroyuki Katayama, Hiroshi Hama, Koji Nagasawa, Hiroshi Kurokawa, Mayu Sugiyama, Ryoko Ando, Masaaki Funata, Nobuyo Yoshida, Misaki Homma, Takanori Nishimura, Megumu Takahashi, Yoko Ishida, Hiroyuki Hioki, Yoshiyuki Tsujihata, Atsushi Miyawaki

Issue&Volume: 2020-05-20

Abstract: Dysfunctional mitochondria accumulate in many human diseases. Accordingly, mitophagy,which removes these mitochondria through lysosomal degradation, is attracting broadattention. Due to uncertainties in the operational principles of conventional mitophagyprobes, however, the specificity and quantitativeness of their readouts are disputable.Thorough investigation of the behaviors and fates of fluorescent proteins inside andoutside lysosomes enabled us to develop an indicator for mitophagy, mito-SRAI. Throughstrict control of its mitochondrial targeting, we were able to monitor mitophagy infixed biological samples more reproducibly than before. Large-scale image-based high-throughputscreening led to the discovery of a hit compound that induces selective mitophagyof damaged mitochondria. In a mouse model of Parkinsons disease, we found that dopaminergicneurons selectively failed to execute mitophagy that promoted their survival withinlesions. These results show that mito-SRAI is an essential tool for quantitative studiesof mitochondrial quality control.

DOI: 10.1016/j.cell.2020.04.025

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30488-8