a chemical screen probing the relationship between mitochondrial content and cell size化学屏幕探索线粒体含量和细胞大小之间的关系.pdfVIP

A Chemical Screen Probing the Relationship between Mitochondrial Content and Cell Size 1,2,3 1 1 1 1 Toshimori Kitami , David J. Logan , Joseph Negri , Thomas Hasaka , Nicola J. Tolliday , 1 4 1,2,3 Anne E. Carpenter , Bruce M. Spiegelman , Vamsi K. Mootha * 1 Broad Institute, Cambridge, Massachusetts, United States of America, 2 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America, 4 Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States of America Abstract The cellular content of mitochondria changes dynamically during development and in response to external stimuli, but the underlying mechanisms remain obscure. To systematically identify molecular probes and pathways that control mitochondrial abundance, we developed a high-throughput imaging assay that tracks both the per cell mitochondrial content and the cell size in confluent human umbilical vein endothelial cells. We screened 28,786 small molecules and observed that hundreds of small molecules are capable of increasing or decreasing the cellular content of mitochondria in a manner proportionate to cell size, revealing stereotyped control of these parameters. However, only a handful of compounds dissociate this relationship. We focus on one such compound, BRD6897, and demonstrate through secondary assays that it increases t