MiP2005: Session 7

Mitochondrial Physiology Network 10.9: 83 (2005) - download pdf


Pathophysiological role of mitochondrial glycerophosphate dehydrogenase.

Zdeněk Drahota, M Vrbacký, P Ješina, T Mráček, J Houštěk

Institute of Physiology and Center of Applied Genomics, Academy of Science of the Czech Republic, Prague, Czech Republic. -  drahota@biomed.cas.cz

    Mitochondrial glycerophosphate dehydrogenase (mGPDH) is an important regulatory device of cell intermediary metabolism. Its activity is very high in several mammalian tissues (brown fat [1], placenta [2], beta cells of pancreas [3]) however, in most tissues its expression is highly down-regulated. In spite of many speculations about its role in various physiological (thermogenesis [4]) and pathological (hyperthyroidism [5], cancer [6]) processes, the significance of remarkable variations of the mGPDH activity in various mammalian tissues is not clear.

    We have reported that mGPDH represents a new site of ROS production in brown fat [6], liver [7] and placental mitochondria [8]. In this communication we present additional data indicating: (a) that ROS production measured by Amplex Red in the presence of Rotenone, Antimycin A and Myxothiazol  is directly connected with mGPDH catalytic  function, (b) that transfer of electrons from mGPDH to CoQ has different characteristics that that from succinate dehydrogenase, (c) that correlation of triiodothyronine concentration  in serum, mRNA level for mGPDH in liver homogenate, mGPDH protein content and mGPDH activity in liver mitochondria after application of a single dose of triiodothyronine to euthyroid rats indicates that this enzyme is quickly eliminated from the mitochondrial membrane when the hormonal signal disappears.

    On the basis of these data potential role of mGPDH in various pathological processes is discussed.

1.  Houstek J, Kopecky J, Drahota Z (1978) Specific properties of brown adipose tissue mitochondrial membrane. Comp.Biochem.Physiol.[B]. 60: 209-214.

2.  Swierczynski J, Scislowski P, Aleksandrowicz Z (1976) High activity of alpha-glycerophosphate oxidation by human placental mitochondria. Biochim. Biophys. Acta. 429: 46-54.

3.  MacDonald MJ, Brown LJ (1996) Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied. Arch. Biochem. Biophys. 326: 79-84.

4.  Lardy H, Kneer N, Bellei M, Bobyleva V (1995) Induction of thermogenic enzymes by DHEA and its metabolites. Ann.N.Y.Acad.Sci. 774: 171-179.

5.  Rauchova H, Zacharova G, Soukup T (2004) Influence of chronically altered thyroid status on the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase in female inbred lewis rats. Horm. Metab. Res. 36(5): 286-90.

6.  Drahota Z, Chowdhury SK, Floryk D, Mracek T, Wilhelm J, Rauchova H, Lenaz G, Houstek J (2002) Glycerophosphate-dependent hydrogen peroxide production by brown adipose tissue mitochondria and its activation by ferricyanide. J. Bioenerg. Biomembr. 34: 105-113.

7.  Jesina P, Kholova D, Bolehovska R, Cervinkova Z, Drahota Z, Houstek J (2004) Glycerophosphate-Dependent Hydrogen Peroxide Production by Rat Liver Mitochondria. Physiol. Res. 53: 305-310.

8.  Honzik T, Drahota Z, Bohm M, Jesina P, Mracek T, Paul J, Zeman J, Houstek J (2005) Specific Properties of Heavy Fraction of Mitochondria from Human-term Placenta - Glycerophosphate-dependent Hydrogen Peroxide Production. Placenta. in press.

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