The position 252 of cytochrome b , involved in a
mitochondrial human pathology, interacts with subunit 9 of the yeast
bc1 complex.
Yann Saint-Georges (1), Nathalie Bonnefoy (1), Jean Paul di Rago
(2), Stephane Chiron (1), Geneviève Dujardin (1)
(1) Centre Génétique Moléculaire, CNRS, Av. de la terrasse, Gif sur
Yvette, 91198, France;
(2) Institut de Biochimie et Genetique Cellulaires du CNRS, Universite
Victor Segalen, Bordeaux 2, 1 rue Camille Saint Saens, 33077 Bordeaux
cedex, France.
The bc1 mitochondrial respiratory complex, is composed of 10
subunits, three of them being catalytic : cytochrome b, encoded
by the mitochondrial genome, the Rieske protein and cytochrome
c1. In humans, the substitution of a glycine by an aspartate at
position 251 of cytochrome b leads to a cardiomyopathy showing
the importance of this region for the respiratory function. This glycine
251 is a conserved residue (position 252 in yeast) located close to the
quinol oxydation site. In this study, we show that the introduction of
the same mutation CYTB-G252D in the yeast cytochrome b
renders the non catalytic subunit Qcr9p of the bc1 complex
essential for respiratory growth. Indeed, the deletion mutant of
QCR9 (qcr9) is only temperature sensitive for respiratory
growth while the double mutant CYTB-G252D qcr9 cannot grow on non
fermentable medium at any temperature. The bc1 complex is
partially assembled in this double mutant but exhibits no detectable
bc1 activity at 28°C. This suggests a strong interaction between
the position 252 of cytochrome b and Qcr9p. In order to better
understand this interaction, we have combined biolistic transformation
and revertant search to identify various cytochrome b mutations
able to restore the respiratory growth of the CYTB-G252D qcr9
double mutant at 28°C. We have determined the effect of these mutations
on the accumulation of the catalytic subunits as well as on the assembly
and the activity of the bc1 complex.
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