Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons during the period of normal programmed cell death

So Yoen Choi, Joo Yeon Kim, Hyun Wook Kim, Bongki Cho, Hyo Min Cho, Ronald W. Oppenheim, Hyun Kim, Im Joo Rhyu, Woong Sun

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mitochondrial morphology is dynamically remodeled by fusion and fission in neurons, and this process is implicated in nervous system development and pathology. However, the mechanism by which mitochondrial dynamics influence neuronal development is less clear. In this study, we found that the length of mitochondria is progressively reduced during normal development of chick embryo motoneurons (MNs), a process partly controlled by a fission-promoting protein, dynamin-related protein 1 (Drp1). Suppression of Drp1 activity by gene electroporation of dominant-negative mutant Drp1 in a subset of developing MNs increased mitochondrial length in vivo, and a greater proportion of Drp1-suppressed MNs underwent programmed cell death (PCD). By contrast, the survival of nontransfected MNs in proximity to the transfected MNs was significantly increased, suggesting that the suppression of Drp1 confers disadvantage during the competition for limited survival signals. Because we also monitored perturbation of neurite outgrowth and mitochondrial membrane depolarization following Drp1 suppression, we suggest that impairments of ATP production and axonal growth may be downstream factors that influence the competition of MNs for survival. Collectively, these results indicate that mitochondrial dynamics are required for normal axonal development and competition-dependent MN PCD.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalFASEB Journal
Volume27
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

Keywords

  • Apoptosis
  • Chick embryo
  • Mitochondria

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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