Control of muscle differentiation by a mitochondria-targeted fluorophore.
During muscle differentiation, mitochondria undergo dramatic changes in their morphology and distribution to prepare for the higher rate of energy consumption. By applying a mitochondria-targeted rosamine library in C2C12 myogenesis, we discovered one compound that controls muscle differentiation. When treated to undifferentiated myoblasts, our selected compound, B25, inhibited myotube formation, and when treated to fully differentiated myotubes, it induced fission of multinucleated myotubes into mononucleated fragments. Compared to myoseverin, which is known for inducing myotube fission by destabilizing microtubules, B25 affects neither microtubule stability nor cell cycle. Further investigation identified that B25 induces myotube fission through the activation of NF-kappaB, which is one of the important signaling pathways linked to skeletal muscle differentiation. So far, the use of small-molecule fluorophores is limited in the discovery of labeling agents or sensors. In addition to their potential as a sensor, here we show the application of fluorescent small molecules in the discovery of a bioactive probe that induces a specific cellular response.
Kim
Yun Kyung
YK
Department of Chemistry, New York University, New York, New York 10003, USA.
Ha
Hyung-Ho
HH
Lee
Jun-Seok
JS
Bi
Xuezhi
X
Ahn
Young-Hoon
YH
Hajar
Siti
S
Lee
Jae-Jung
JJ
Chang
Young-Tae
YT
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005456:Fluorescent Dyes / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008970:Molecular Weight; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D011687:Purines / Q000494:pharmacology; D051381:Rats
D005456:Fluorescent Dyes; D011687:Purines; C407365:myoseverin