Chinopoulos 2018 MiP2018

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Christos Chinopoulos
Exclusive neuronal expression of KGDHC-specific subunits in the adult human brain cortex despite pancellular protein lysine succinylation.

Link: MiP2018

Dobolyi A, Bago A, Palkovits M, Nemeria NS, Jordan F, Doczi J, Ambrus A, Adam-Vizi V, Chinopoulos C (2018)

Event: MiP2018

COST Action MitoEAGLE

Ketoglutarate dehydrogenase complex (KGDHC) consists of three different subunits encoded by OGDH (or OGDHL), DLST and DLD, combined in different stoichiometries. DLD subunit is shared between KGDHC and pyruvate dehydrogenase complex, branched-chain alpha-keto acid dehydrogenase complex and the glycine cleavage system. Despite KGDHC’s implication in neurodegenerative diseases, cell-specific localization of its subunits in the adult human brain has never been investigated. Here we show that immunoreactivity of all known isoforms of OGDHL, OGDH and DLST in surgical human cortical tissue samples was present exclusively in neurons identified by their morphology and visualized by double labeling with fluorescent Nissl, while being absent from glia expressing GFAP, myelin basic protein, or IBA1. In contrast, DLD immunoreactivity was evident in both neurons and glia. Specificity of anti-KGDHC subunits antisera was verified by a decrease in staining of siRNA-treated human cancer cell lines directed against the respective coding gene products. In human fibroblasts, immunoreactivity of KGDHC subunits co-localized >99 % with mitotracker orange while western blotting of 63 post mortem brain samples and purified recombinant proteins afforded further assurance regarding antisera monospecificity. Surprisingly, protein lysine succinylation was immunohistochemically evident in all cortical cells; this was unexpected because this posttranslational modification requires succinyl-CoA, the product of KGDHC. Mindful that glia of the human brain cortex also lack succinate-CoA ligase, an enzyme producing succinyl-CoA when operating in reverse, protein lysine succinylation in these cells must exclusively rely on propionate and/or ketone body metabolism or some other yet to be discovered pathway encompassing succinyl-CoA.


Bioblast editor: Plangger M, Kandolf G O2k-Network Lab: HU Budapest Chinopoulos C


Labels: MiParea: nDNA;cell genetics  Pathology: Cancer 

Organism: Human  Tissue;cell: Nervous system, Fibroblast 





Affiliations

Dobolyi A(1,2), Bago A(3), Palkovits M(1), Nemeria NS(4), Jordan F(4), Doczi J(5), Ambrus A(5,6), Adam-Vizi V(5,6), Chinopoulos C(5)

  1. MTA-ELTE Lab Molecular Systems Neurobiology, Inst Biology, Hungarian Academy Sciences Eotvos Lorand Univ
  2. Dept Anatomy, Histology Embryology, Semmelweis Univ
  3. National Inst Neurosurgery; Budapest, Hungary
  4. Dept Chemistry, Rutgers Univ, Newark, NJ, USA
  5. Dept Medical Biochemistry
  6. MTA-SE Lab Neurobiochemistry; Semmelweis Univ, Budapest, Hungary. - chinopoulos.christos@eok.sote.hu