Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the cerebral cortex suggests the absence of matrix substrate-level phosphorylation in glial cells of the human brain

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• 作者：Arpád Dobolyi ; Attila G. Bagó ; Aniko Gál…
• 关键词：Krebs cycle ; Citric acid cycle ; Substrate ; level phosphorylation ; Succinyl CoA ligase ; Microglia ; Oligodendrocytes
• 刊名：Journal of Bioenergetics and Biomembranes
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：47
• 期：1-2
• 页码：33-41
• 全文大小：6,231 KB
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• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Bioorganic Chemistry
  Biochemistry
  Animal Anatomy, Morphology and Histology
  Animal Biochemistry
  Organic Chemistry
  
• 出版者：Springer New York
• ISSN：1573-6881

文摘

We have recently shown that the ATP-forming SUCLA2 subunit of succinyl-CoA ligase, an enzyme of the citric acid cycle, is exclusively expressed in neurons of the human cerebral cortex; GFAP- and S100-positive astroglial cells did not exhibit immunohistoreactivity or in situ hybridization reactivity for either SUCLA2 or the GTP-forming SUCLG2. However, Western blotting of post mortem samples revealed a minor SUCLG2 immunoreactivity. In the present work we sought to identify the cell type(s) harboring SUCLG2 in paraformaldehyde-fixed, free-floating surgical human cortical tissue samples. Specificity of SUCLG2 antiserum was supported by co-localization with mitotracker orange staining of paraformaldehyde-fixed human fibroblast cultures, delineating the mitochondrial network. In human cortical tissue samples, microglia and oligodendroglia were identified by antibodies directed against Iba1 and myelin basic protein, respectively. Double immunofluorescence for SUCLG2 and Iba1 or myelin basic protein exhibited no co-staining; instead, SUCLG2 appeared to outline the cerebral microvasculature. In accordance to our previous work there was no co-localization of SUCLA2 immunoreactivity with either Iba1 or myelin basic protein. We conclude that SUCLG2 exist only in cells forming the vasculature or its contents in the human brain. The absence of SUCLA2 and SUCLG2 in human glia is in compliance with the presence of alternative pathways occurring in these cells, namely the GABA shunt and ketone body metabolism which do not require succinyl CoA ligase activity, and glutamate dehydrogenase 1, an enzyme exhibiting exquisite sensitivity to inhibition by GTP.