Dynamin-related protein 1 controls the migration and neuronal differentiation of subventricular zone-derived neural progenitor cells

Hyun Jung Kim, Mohammed R. Shaker, Bongki Cho, Hyo Min Cho, Hyun Kim, Joo Yeon Kim, Woong Sun

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Article number15962
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Oct 30

Bibliographical note

Funding Information:
This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, the ICT & Future Planning (NRF-2012M3A9C6049933, NRF-2011-0019210, NRF-2015M3C7A1028790 and NRF-2013R1A1A3011896), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) that is funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3347).

ASJC Scopus subject areas

  • General

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