Chinopoulos 2012 Abstract Bioblast

Dobolyi A, Ostergaard E, Bago AG, Palkovits M, Adam-Vizi V, Chinopoulos C (2012) Exclusive neuronal expression of SUCLA2 in the human brain. Mitochondr Physiol Network 17.12.

Link: MiPNet17.12 Bioblast 2012 - Open Access

Chinopoulos C (2012)

Event: Bioblast 2012

SUCLA2 encodes for the ADP-forming β-subunit (A-SUCL-β) of succinyl CoA ligase, an enzyme of the citric acid cycle [1]. Mutations in SUCLA2 lead to a mitochondrial disorder associated with mitochondrial DNA depletion [2]. This mitochondrial disorder manifests as neonatal encephalomyopathy exhibiting dystonia, deafness and pronounced lesions in the basal ganglia [3]. Despite that a SUCLA2 gene defect results in distinct brain pathology, precise localization of the encoded protein has never been investigated. Here we show that the immunoreactivity of A-SUCL-β in the human cerebral cortex was present exclusively in neurons, identified by their morphology and visualized by double labelling with a fluorescent Nissl dye. The A-SUCL-β immunoreactivity co-localized >99% with that of the d-subunit of the mitochondrial F₀-F₁ ATP synthase. Specificity of the anti-A-SUCL-β antiserum was verified by the absence of labelling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL-β immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex (Fig. 1). Therefore, all encephalopathic features of the disease emerging by mutations in this gene originate solely from the neuronal cell population.

1. Lambeth DO, Tews KN, Adkins S, Frohlich D, Milavetz BI (2004) Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues. J Biol Chem 279: 36621-36624.
2. Ostergaard E (2008) Disorders caused by deficiency of succinate-CoA ligase. J Inherit Metab Dis 31: 226-229.
3. Carrozzo R, Onisi-Vici C, Steuerwald U, Lucioli S, Deodato F, Di GS, Bertini E, Franke B, Kluijtmans LA, Meschini MC, Rizzo C, Piemonte F, Rodenburg R, Santer R, Santorelli FM, van RA, Vermunt-de KD, Morava E, Wevers RA (2007) SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain 130: 862-874.

• Keywords: SUCLA2, Mitochondrial disorder, Cortex

• O2k-Network Lab: HU Budapest Chinopoulos C

Labels:

Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Nervous system 

Affiliations and author contributions

Arpád Dobolyi (1), Elsebet Ostergaard (2), Attila G. Bagó (1,3), Miklós Palkovits (1,4), Vera Adam-Vizi (5) and Christos Chinopoulos (5)

(1) Department of Anatomy, Histology and Embryology, Semmelweis University, Hungary; Email: [email protected]

(2) Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Denmark

(3) National Institute of Neurosurgery, Hungary

(4) Human Brain Tissue Bank, Semmelweis University, Hungary

(5) Department of Medical Biochemistry, Semmelweis University, Hungary

Figure 1

Co-localization of fluorescent Nissl staining the cytosol of neurons (red)

and the ADP-forming β-subunit (A-SUCL-β)

of succinyl CoA ligase (green-->yellow) in human temporal cortex.

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