Abstract：
:Dysfunctional mitochondria accumulate in many human diseases. Accordingly, mitophagy, which removes these mitochondria through lysosomal degradation, is attracting broad attention. Due to uncertainties in the operational principles of conventional mitophagy probes, however, the specificity and quantitativeness of their readouts are disputable. Thorough investigation of the behaviors and fates of fluorescent proteins inside and outside lysosomes enabled us to develop an indicator for mitophagy, mito-SRAI. Through strict control of its mitochondrial targeting, we were able to monitor mitophagy in fixed biological samples more reproducibly than before. Large-scale image-based high-throughput screening led to the discovery of a hit compound that induces selective mitophagy of damaged mitochondria. In a mouse model of Parkinsons disease, we found that dopaminergic neurons selectively failed to execute mitophagy that promoted their survival within lesions. These results show that mito-SRAI is an essential tool for quantitative studies of mitochondrial quality control.
journal_name
Celljournal_title
Cellauthors
Katayama H,Hama H,Nagasawa K,Kurokawa H,Sugiyama M,Ando R,Funata M,Yoshida N,Homma M,Nishimura T,Takahashi M,Ishida Y,Hioki H,Tsujihata Y,Miyawaki Adoi
10.1016/j.cell.2020.04.025subject
Has Abstractpub_date
2020-05-28 00:00:00pages
1176-1187.e16issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(20)30488-8journal_volume
181pub_type
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