Mitochondrial distribution of neuroglobin and its response to oxygen-glucose deprivation in primary-cultured mouse cortical neurons.
Neuroglobin (Ngb) is a new member of the globin family and a novel endogenous neuroprotective molecule, but its neuroprotective mechanisms remain largely undefined. Previous studies suggest Ngb is both physically and functionally related to mitochondria, however without direct evidence. Our recent discovery has shown that Ngb can physically interact with a number of mitochondrial proteins. In this study we aimed to define the physical interaction between Ngb and mitochondria by determining whether there is a mitochondrial distribution of Ngb under both physiological-resting and pathological oxygen-glucose deprivation (OGD) conditions. Western blot for the first time revealed a small portion of Ngb was physically localized in mitochondria, and the relative mitochondrial Ngb level was significantly increased after OGD in primary-cultured mouse cortical neurons, indicating a translocation of Ngb into mitochondria. Complementary approaches including confocal imaging and immuno-electron microscopy confirmed Ngb distribution in mitochondria under both basal-resting condition and OGD. Inhibitors of mitochondria permeability transition pore (mPTP) and Voltage-Dependent Anion Channel (VDAC) blocked OGD-induced increase of mitochondrial Ngb level, demonstrating a possible role of mPTP in Ngb's mitochondrial translocation. We further found that Ngb overexpression-conferred neuroprotection was correlated with increased mitochondrial Ngb level, suggesting the mitochondria distribution of Ngb is clearly associated with and may contribute to Ngb's neuroprotection.
Neuroprotection Research Laboratory, Departments of Neurology and Radiology, Massachusetts General Hospital, Charlestown, MA, USA. zyu@partners.org
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Z
Yu
J
J
Xu
N
N
Liu
Y
Y
Wang
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X
Li
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S
Pallast
K
K
van Leyen
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X
Wang
D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005914:Globins / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology*
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D005947:Glucose