title: Dynamin-related protein 1 controls the migration and neuronal differentiation of subventricular zone-derived neural progenitor cells.
abstract: Mitochondria are important in many essential cellular functions, including energy production, calcium homeostasis, and apoptosis. The organelles are scattered throughout the cytoplasm, but their distribution can be altered in response to local energy demands, such as cell division and neuronal maturation. Mitochondrial distribution is closely associated with mitochondrial fission, and blocking the fission-promoting protein dynamin-related protein 1 (Drp1) activity often results in mitochondrial elongation and clustering. In this study, we observed that mitochondria were preferentially localized at the leading process of migratory adult neural stem cells (aNSCs), whereas neuronal differentiating cells transiently exhibited perinuclear condensation of mitochondria. Inhibiting Drp1 activity altered the typical migratory cell morphology into round shapes while the polarized mitochondrial distribution was maintained. With these changes, aNSCs failed to migrate, and neuronal differentiation was prevented. Because Drp1 blocking also impaired the mitochondrial membrane potential, we tested whether supplementing with L-carnitine, a compound that restores mitochondrial membrane potential and ATP synthesis, could revert the defects induced by Drp1 inhibition. Interestingly, L-carnitine fully restored the aNSC defects, including cell shrinkage, migration, and impaired neuronal differentiation. These results suggest that Drp1 is required for functionally active mitochondria, and supplementing with ATP can restore the defects induced by Drp1 suppression.
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Shaker
authors.affiliation: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
authors.forename: Bongki
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Cho
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 136-705, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity; D002478:Cells, Cultured; D034281:Dynamins / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D009840:Oligomycins; D052999:Quinazolinones; C486391:Dnm1l protein, mouse; D034281:Dynamins; D002331:Carnitine