PMID- 27567688
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20181113
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 76
DP  - 2016 Oct
TI  - Mitochondrial dynamics following global cerebral ischemia.
PG  - 68-75
LID - S1044-7431(16)30132-4 [pii]
LID - 10.1016/j.mcn.2016.08.010 [doi]
AB  - Global brain ischemia/reperfusion induces neuronal damage in vulnerable brain 
      regions, leading to mitochondrial dysfunction and subsequent neuronal death. 
      Induction of neuronal death is mediated by release of cytochrome c (cyt c) from 
      the mitochondria though a well-characterized increase in outer mitochondrial 
      membrane permeability. However, for cyt c to be released it is first necessary 
      for cyt c to be liberated from the cristae junctions which are gated by Opa1 
      oligomers. Opa1 has two known functions: maintenance of the cristae junction and 
      mitochondrial fusion. These roles suggest that Opa1 could play a central role in 
      both controlling cyt c release and mitochondrial fusion/fission processes during 
      ischemia/reperfusion. To investigate this concept, we first utilized in vitro 
      real-time imaging to visualize dynamic changes in mitochondria. Oxygen-glucose 
      deprivation (OGD) of neurons grown in culture induced a dual-phase mitochondrial 
      fragmentation profile: (i) fragmentation during OGD with no apoptosis activation, 
      followed by fusion of mitochondrial networks after reoxygenation and a (ii) 
      subsequent extensive fragmentation and apoptosis activation that preceded cell 
      death. We next evaluated changes in mitochondrial dynamic state during 
      reperfusion in a rat model of global brain ischemia. Evaluation of mitochondrial 
      morphology with confocal and electron microscopy revealed a similar induction of 
      fragmentation following global brain ischemia. Mitochondrial fragmentation 
      aligned temporally with specific apoptotic events, including cyt c release, 
      caspase 3/7 activation, and interestingly, release of the fusion protein Opa1. 
      Moreover, we uncovered evidence of loss of Opa1 complexes during the progression 
      of reperfusion, and electron microscopy micrographs revealed a loss of cristae 
      architecture following global brain ischemia. These data provide novel evidence 
      implicating a temporal connection between Opa1 alterations and dysfunctional 
      mitochondrial dynamics following global brain ischemia.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kumar, Rita
AU  - Kumar R
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States; Department of 
      Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United 
      States.
FAU - Bukowski, Melissa J
AU  - Bukowski MJ
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States; Department of 
      Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United 
      States.
FAU - Wider, Joseph M
AU  - Wider JM
AD  - Cardiovascular Research Institute, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Department of Physiology, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States.
FAU - Reynolds, Christian A
AU  - Reynolds CA
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States; Department of 
      Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United 
      States.
FAU - Calo, Lesley
AU  - Calo L
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States; Department of 
      Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United 
      States.
FAU - Lepore, Bradley
AU  - Lepore B
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States.
FAU - Tousignant, Renee
AU  - Tousignant R
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States.
FAU - Jones, Michelle
AU  - Jones M
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States.
FAU - Przyklenk, Karin
AU  - Przyklenk K
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States; Department of 
      Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United 
      States.
FAU - Sanderson, Thomas H
AU  - Sanderson TH
AD  - Department of Emergency Medicine, Wayne State University School of Medicine, 
      Detroit, MI 48201, United States; Cardiovascular Research Institute, Wayne State 
      University School of Medicine, Detroit, MI 48201, United States. Electronic 
      address: tsanders@med.wayne.edu.
LA  - eng
GR  - R01 NS076715/NS/NINDS NIH HHS/United States
GR  - R01 NS091242/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160825
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (Opa1 protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Brain Ischemia/*metabolism
MH  - CA1 Region, Hippocampal/blood supply/metabolism
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Cells, Cultured
MH  - GTP Phosphohydrolases/metabolism
MH  - Male
MH  - Mice
MH  - Mitochondria/metabolism/ultrastructure
MH  - *Mitochondrial Dynamics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism
PMC - PMC5056829
MID - NIHMS814274
OTO - NOTNLM
OT  - Brain ischemia
OT  - Mitochondrial dynamics
OT  - Opa1
OT  - Reperfusion
EDAT- 2016/08/29 06:00
MHDA- 2018/01/13 06:00
PMCR- 2017/10/01
CRDT- 2016/08/29 06:00
PHST- 2015/11/20 00:00 [received]
PHST- 2016/08/19 00:00 [revised]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/08/29 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2016/08/29 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - S1044-7431(16)30132-4 [pii]
AID - 10.1016/j.mcn.2016.08.010 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2016 Oct;76:68-75. doi: 10.1016/j.mcn.2016.08.010. Epub 2016 
      Aug 25.