Mutations in mitochondrial genes are
associated with a growing number of diseases in human beings.
More than 100 point mutations have been reported.1 These genetic
lesions are located in genes coding for subunits of the respiratory
complexes-complex I, complex III, cytochrome oxidase, and ATPase-and
for the mitochondrial translation apparatus: rRNAs and tRNAs.
To characterise the effects of these disease-related mutations,
we use yeast as a model system. Since yeast is amenable to mitochondrial
transformation, designed mutations can be introduced in its
mitochondrial genome. Yeast mutants harbouring the model human
mutations can then be used to characterise the deleterious effect
of these mutations and to explore ways of restoring the respiratory
function impaired by these genetic lesions (figure 1).
Inhibitors of the respiratory-chain complex bc1 are widely used
in medicine and in agriculture to control pathogens. Mutations
in the mitochondrially-encoded cytochrome b gene have been reported
in human and plant parasites that are resistant to treatment
by these inhibitors.
To provide easy-to-use models for study of acquired resistance,
we introduce inhibitor-resistant mutations into yeast cytochrome
b. We then use the yeast strains with modified bc1 complex to
characterise the effects of the mutations on respiratory function
and cross-resistance to other drugs (figure 2).