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 language | English |
|---|---|
| Pages (from-to) | 51-62 |
| Number of pages | 12 |
| Journal | FASEB Journal |
| Volume | 27 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Jan 1 |
Fingerprint
Keywords
- Apoptosis
- Chick embryo
- Mitochondria
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
Cite this
Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons during the period of normal programmed cell death. / Choi, So Yoen; Kim, Joo Yeon; Kim, Hyun Wook; Cho, Bongki; Cho, Hyo Min; Oppenheim, Ronald W.; Kim, Hyun; Rhyu, Im Joo; Sun, Woong.
In: FASEB Journal, Vol. 27, No. 1, 01.01.2013, p. 51-62.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Drp1-mediated mitochondrial dynamics and survival of developing chick motoneurons during the period of normal programmed cell death
AU - Choi, So Yoen
AU - Kim, Joo Yeon
AU - Kim, Hyun Wook
AU - Cho, Bongki
AU - Cho, Hyo Min
AU - Oppenheim, Ronald W.
AU - Kim, Hyun
AU - Rhyu, Im Joo
AU - Sun, Woong
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Chick embryo
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=84871857529&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871857529&partnerID=8YFLogxK
U2 - 10.1096/fj.12-211920
DO - 10.1096/fj.12-211920
M3 - Article
C2 - 22997225
AN - SCOPUS:84871857529
VL - 27
SP - 51
EP - 62
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 1530-6860
IS - 1
ER -