scholarly journals Differential ROS-Mediated Phosphorylation of Drp1 in Mitochondrial Fragmentation Induced by Distinct Cell Death Conditions in Cerebellar Granule Neurons

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Carolina Cid-Castro ◽  
Julio Morán
Keyword(s):  
Cell Death ◽  
Neuronal Death ◽  
Mitochondrial Fission ◽  
Cerebellar Granule Neurons ◽  
Mitochondrial Morphology ◽  
Granule Neurons ◽  
Ros Production ◽  
Mitochondrial Fragmentation ◽  
Cerebellar Granule ◽  
Mitochondrial Ros

Reactive oxygen species (ROS) production has been associated with neuronal death. ROS are also involved in mitochondrial fission, which is mediated by Dynamin-related protein 1 (Drp1). The regulation of mitochondrial fragmentation mediated by Drp1 and its relationship to mitochondrial ROS (mtROS) in neuronal death have not been completely clarified. The aim of this study is to evaluate the role of mtROS in cell death and their involvement in the activation of Drp1 and mitochondrial fission in a model of cell death of cultured cerebellar granule neurons (CGN). Neuronal death of CGN induced by potassium deprivation (K5) and staurosporine (ST) triggers mitochondrial ROS production and mitochondrial fragmentation. K5 condition evoked an increase of Drp1 phosphorylation at Ser616, but ST treatment led to a decrease of Drp1 phosphorylation. Moreover, the death of CGN induced by both K5 and ST was markedly reduced in the presence of MitoTEMPO; however, mitochondrial morphology was not recovered. Here, we show that the mitochondria are the initial source of ROS involved in the neuronal death of CGN and that mitochondrial fragmentation is a common event in cell death; however, this process is not mediated by Drp1 phosphorylation at Ser616.

scholarly journals Fzo1, a Protein Involved in Mitochondrial Fusion, Inhibits Apoptosis

2004 ◽  
Vol 279 (50) ◽  
pp. 52726-52734 ◽  
Author(s):  
Rie Sugioka ◽  
Shigeomi Shimizu ◽  
Yoshihide Tsujimoto
Keyword(s):  
Cell Death ◽  
Conformational Changes ◽  
Apoptotic Cell ◽  
Mitochondrial Fission ◽  
Apoptotic Cell Death ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Human Homolog ◽  
Mitochondrial Fragmentation ◽  
Apoptotic Death

Mitochondrial morphology and physiology are regulated by the processes of fusion and fission. Some forms of apoptosis are reported to be associated with mitochondrial fragmentation. We showed that overexpression of Fzo1A/B (rat) proteins involved in mitochondrial fusion, or silencing of Dnm1 (rat)/Drp1 (human) (a mitochondrial fission protein), increased elongated mitochondria in healthy cells. After apoptotic stimulation, these interventions inhibited mitochondrial fragmentation and cell death, suggesting that a process involved in mitochondrial fusion/fission might play a role in the regulation of apoptosis. Consistently, silencing of Fzo1A/B or Mfn1/2 (a human homolog of Fzo1A/B) led to an increase of shorter mitochondria and enhanced apoptotic death. Overexpression of Fzo1 inhibited cytochromecrelease and activation of Bax/Bak, as assessed from conformational changes and oligomerization. Silencing of Mfn or Drp1 caused an increase or decrease of mitochondrial sensitivity to apoptotic stimulation, respectively. These results indicate that some of the proteins involved in mitochondrial fusion/fission modulate apoptotic cell death at the mitochondrial level.

Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

2009 ◽  
Vol 87 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Yutaka Ikeno ◽  
So-hyun Cheon ◽  
Naoko Konno ◽  
Ayako Nakamura ◽  
Katsuhiko Kitamoto ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cerebellar Granule

Apoptotic cell death of cerebellar granule neurons in genetically ataxia (ax) mice

2000 ◽  
Vol 288 (3) ◽  
pp. 167-170 ◽  
Author(s):  
Makoto Ohgoh ◽  
Kazuto Yamazaki ◽  
Hiroo Ogura ◽  
Yukio Nishizawa ◽  
Isao Tanaka
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cerebellar Granule

scholarly journals Enhanced cell death in MeCP2 null cerebellar granule neurons exposed to excitotoxicity and hypoxia

Neuroscience ◽  
2007 ◽  
Vol 150 (3) ◽  
pp. 563-574 ◽  
Author(s):  
J.C. Russell ◽  
M.E. Blue ◽  
M.V. Johnston ◽  
S. Naidu ◽  
M.A. Hossain
Keyword(s):  
Cell Death ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cerebellar Granule

scholarly journals Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP

1993 ◽  
Vol 90 (23) ◽  
pp. 10989-10993 ◽  
Author(s):  
S R D'Mello ◽  
C Galli ◽  
T Ciotti ◽  
P Calissano
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Growth Factor ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Insulin Like Growth Factor ◽  
Cerebellar Granule ◽  
Factor I ◽  
Growth Factor I ◽  
Low K

High levels of extracellular K+ ensure proper development and prolong survival of cerebellar granule neurons in culture. We find that when switched from a culture medium containing high K+ (25 mM) to one containing a low but more physiological K+ concentration (5 mM), differentiated granule neurons degenerate and die. Death induced by low K+ is due to apoptosis (programmed cell death), a form of cell death observed extensively in the developing nervous system and believed to be necessary for proper neurogenesis. The death process is accompanied by cleavage of genomic DNA into internucleosome-sized fragments, a hallmark of apoptosis. Inhibitors of transcription and translation suppress apoptosis induced by low K+, suggesting the necessity for newly synthesized gene products for activation of the process. Death can be prevented by insulin-like growth factor I but not by several other growth/neurotrophic factors. cAMP but not the protein kinase C activator phorbol 12-myristate 13-acetate can also support survival in low K+. In view of the large numbers of granule neurons that can be homogeneously cultured, our results offer the prospect of an excellent model system to study the mechanisms underlying apoptosis in the central nervous system and the suppression of this process by survival factors such as insulin-like growth factor I.

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