Increased synthesis and decreased stability of mitochondrial translation products in yeast as a result of loss of mitochondrial (NAD(+))-dependent isocitrate dehydrogenase.
We have previously demonstrated that the yeast Krebs cycle enzyme NAD(+)-dependent isocitrate dehydrogenase (Idh) binds specifically and with high affinity to the 5'-untranslated leader sequences of mitochondrial mRNAs in vitro and have proposed a role for the enzyme in the regulation of mitochondrial translation [Elzinga, S.D.J. et al. (2000) Curr. Genet., in press]. Although our studies initially failed to reveal any consistent correlation between idh disruption and mitochondrial translational activity, it is now apparent that compensatory extragenic suppressor mutations readily accumulate in idh disruption strains thereby masking mutant behaviour. Now, pulse-chase protein labelling of isolated mitochondria from an Idh disruption mutant lacking suppressor mutations reveals a strong (2-3-fold) increase in the synthesis of mitochondrial translation products. Strikingly, the newly synthesised proteins are more short-lived than in mitochondria from wild-type cells, their degradation occurring with a 2-3-fold reduced half-life. Enhanced degradation of translation products is also a feature of yeast mutants in which tethering/docking of mitochondrial mRNAs is disturbed. We therefore suggest that binding of Idh to mitochondrial mRNAs may suppress inappropriate translation of mitochondrial mRNAs.
de Jong
L
L
Section for Molecular Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands.
Elzinga
S D
SD
McCammon
M T
MT
Grivell
L A
LA
van der Spek
H
H
D000251:Adenosine Triphosphatases / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases; D009154:Mutation; D009243:NAD / Q000502:physiology; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
D005656:Fungal Proteins; D009243:NAD; D007521:Isocitrate Dehydrogenase; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases