Mitochondrial turnover is required for proper cellular function. Both mitochondrial biogenesis and mitophagy are impaired in several degenerative and age-related diseases. The search for mitophagy activators recently emerged as a new therapeutical approach; however, there is a lack in suitable tools to follow mitochondrial turnover in a high-throughput manner. We demonstrate that the fluorescent protein, MitoTimer, is a reliable and robust probe to follow mitochondrial turnover. The screening of 15 000 small molecules led us to two chemically-related benzothiophenes that stimulate basal mitophagy in the beta-cell line, INS1. Enhancing basal mitophagy was associated with improved mitochondrial function, higher Complex I activity and Complex II and III expressions in INS1 cells, as well as better insulin secretion performance in mouse islets. The possibility of further enhancing mitophagy in the absence of mitochondrial stressors points to the existence of a ‘basal mitophagy spare capacity'. To this end, we found two small molecules that can be used as models to better understand the physiological regulation of mitophagy.
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Cover Image
Cover Image
Prevotella intermedia PinO protein is homologous to Porphyromonas gingivalis HmuY hemophore-like protein, but binds haem with a different haem coordination mode and preferentially in reducing environment. Molecular dynamics stimulations of the haem iron coordination by the PinO suggest engagement of one methionine residue, with interchangeable participation of two additional methionine residues. For more information, see the article by Bielecki and colleagues on pp. 381–405. Image courtesy of Teresa Olczak.
MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy
Fernanda M. Cerqueira, Noga Kozer, Anton Petcherski, Boris M. Baranovski, Dane Wolf, Essam A. Assali, Yaelle Roth, Roi Gazit, Haim Barr, Eli C. Lewis, Guy Las, Orian S. Shirihai; MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy. Biochem J 31 January 2020; 477 (2): 461–475. doi: https://doi.org/10.1042/BCJ20190616
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