Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase

[en] Decreased thiamine and reduced activity of thiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenase (OGDH) cause neurodegeneration. We hypothesized on concerted cell-specific regulation of the thiamine metabolism and ThDP-dependent reactions. We identified a smaller thiamine pool, a lower expression of the mitochondrial ThDP transporter, and a higher expression of OGDH in rat astrocytes versus neuroblastoma N2A. According to the data, the astrocytic OGDH may be up-regulated by an increase in intracellular ThDP, while the neuroblastomal OGDH functions at full ThDP saturation. Indeed, in rat astrocytes and brain cortex, OGDH inhibition by succinyl phosphonate (SP) enlarged the pool of thiamine compounds. Increased ThDP level in response to the OGDH inhibition presumably up-regulated the enzyme to compensate for a decrease in reducing power which occurred in SP-treated astrocytes. Under the same SP treatment of N2A cells, their thiamine pool and reducing power were unchanged, although SP action was evident from accumulation of glutamate. The presented data indicate that functional interplay between OGDH, other proteins of the tricarbocylic acid cycle and proteins of thiamine metabolism is an important determinant of physiology-specific networks and their homeostatic mechanisms.

Research center :

Giga-Neurosciences - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Mkrtchyan, Garik

Graf, Anastasia

Bettendorff, Lucien ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique

Bunik, Victoria

Language :

English

Title :

Cellular thiamine status is coupled to function of mitochondrial 2-oxoglutarate dehydrogenase

Publication date :

2016

Journal title :

Neurochemistry International

ISSN :

0197-0186

Publisher :

Elsevier Science

Volume :

101

Pages :

66-75

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]

Available on ORBi :

since 18 October 2016

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