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HIV‐1 protein Vpr causes gross mitochondrial dysfunction in the yeast Saccharomyces cerevisiae
Author(s) -
Macreadie Ian G,
Thorburn David R,
Kirby Denise M,
Castelli Laura A,
de Rozario Nicole L,
Azad Ahmed A
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00542-5
Subject(s) - saccharomyces cerevisiae , yeast , mitochondrion , biology , respiratory chain , microbiology and biotechnology , biochemistry , gene
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.