Distinct intracellular localization of Gpd1p and Gpd2p, the two yeast isoforms of NAD+-dependent glycerol-3-phosphate dehydrogenase, explains their different contributions to redox-driven glycerol production
Journal article, 2004
During anaerobiosis Saccharomyces cerevisiae strongly increases glycerol production to provide for non-respiratory oxidation of NADH to NAD(+). We here report that respiratory-deficient cells become strictly dependent on the Gpd2p isoform of the NAD(+)-linked glycerol-3-phosphate dehydrogenase (Gpd). The growth inhibition of respiratory incompetent cox18Delta cells lacking GPD2 is reversed by the addition of acetoin, an alternative sink for NADH oxidation. Growth is also restored by addition of lysine or glutamic acid/glutamine, the synthesis of which involves production of mitochondrial NADH. Lysine produced a stronger growth stimulating effect than glutamic acid consistent with an upregulated expression of the IDP3 gene for peroxisomal synthesis of the glutamate precursor alpha-ketoglutarate. Gpd2p is known to be a cytosolic protein but possesses a classical mitochondrial presequence, which we show is sufficient for mitochondrial targeting. A partial mitochondrial localization of Gpd2p will provide for establishment of intramitochondrial redox balance under non-respiratory conditions. Gpd1p, the other Gpd isoform, is partly cytosolic and partly peroxisomal and becomes more strictly peroxisomal in respiratory-deficient mutants. The different cellular distribution of Gpd1p and Gpd2p thus appears to be the main reason Gpd1p cannot substitute for Gpd2p in cox18Deltagpd2Delta cells, despite similar kinetic characteristics of the two iso-enzymes.
genetics
Mitochondria
genetics
Glycerol
Amino Acids
Gene Expression Regulation
enzymology
Acetoin
enzymology
Saccharomyces cerevisiae
Isoenzymes
Glycerol-3-Phosphate Dehydrogenase (NAD+)
Enzymologic
metabolism
Glycerolphosphate Dehydrogenase
metabolism
Cytosol
genetics
Gene Expression Regulation
enzymology
Aerobiosis
growth & development
metabolism
Fungal
metabolism
Oxidation-Reduction
metabolism
Author
Åsa Valadi
University of Gothenburg
Katarina Granath
University of Gothenburg
Lena Gustafsson
Chalmers, Department of Chemistry and Bioscience, Molecular Biotechnology
Lennart Adler
University of Gothenburg
Journal of Biological Chemistry
0021-9258 (ISSN) 1083-351X (eISSN)
Vol. 279 38 39677-39685Subject Categories
Biological Sciences
DOI
10.1074/jbc.M403310200
PubMed
15210723