HIV-1 protein Vpr causes gross mitochondrial dysfunction in the yeast Saccharomyces cerevisiae.
The biological effects of the HIV-1 accessory protein, Vpr, have been studied in yeast expression systems. In our previous study [1], employing the pCUP1-vpr copper-inducible expression cassette, Vpr was shown to cause growth arrest and structural defects. In this study yeast constitutively expressing vpr, through elevated copy number and/or elevated transcription levels, displayed no growth arrest in fermentative growth conditions while Vpr was produced at much lower levels than in the inducible expression system. However, such cells were respiratory deficient and unable to utilise ethanol or glycerol as the sole carbon source. They exhibited gross mitochondrial dysfunction displayed in the loss of respiratory chain complex I, II, III, IV and citrate synthase activities. The effects on mitochondria required a C-terminal domain of Vpr that contains a conserved amino acid sequence motif HFRIGCRHSRIG. These results suggest that the widely observed phenomenon of 'Vpr-induced growth arrest' in human cells could be due to mitochondrial dysfunction.
Macreadie
I G
IG
Biomolecular Research Institute, Parkville, Victoria, Australia. ianm@mel.dbe.csiro.au
Thorburn
D R
DR
Kirby
D M
DM
Castelli
L A
LA
de Rozario
N L
NL
Azad
A A
AA
D016336:Gene Products, vpr / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics; D015497:HIV-1; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism; D014162:Transfection; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D011993:Recombinant Fusion Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D005982:Glutathione Transferase