A mitochondrial mutant strain of D. subobscura has two mitochondrial genome populations (heteroplasmy): the first (20-30% of the population, 15.9 kb) is the same as could be found in the wild type; the second (70-80% of the population, 11 kb) has lost by deletion several genes coding for complex I and III subunits, and four tRNAs. In human pathology, this kind of mutation has been correlated with severe diseases such as the Kearns-Sayre syndrome, but the mutant strain, does not seem to be affected by the mutation (1). Studies reported here show that: a) Transcripts from genes not concerned by the mutation are present at the same level in both strains. b) In contrast, transcript concentrations from genes involved in the deletion are significantly decreased (30-50%) in the mutant. c) Deleted DNA was expressed as shown by the detection of the fusion transcript. d) The mtDNA/nuc.DNA ratio is 1.5 times higher in the mutant strain than in the wild type. The mutation leads to change in the transcript level equilibrium. The apparent innocuousness of the mutation may suggest some post-transcriptional compensation mechanisms. This drosophila strain is an interesting model to study the consequence of this type of mitochondrial genome deletion.

A mutant strain of Drosophila subobscura possesses two mitochondrial genome types: a minority population (20%) identical to the wild strain mtDNA (15.9 kb), and a largely predominant population (80%) of shorter genomes (10.9 kb), presenting a deletion of more than 30% of its coding region. Study of tissular distribution of heteroplasmy shows it to be identical--about 80%--in the head (nervous tissue) and thorax (muscles). On the other hand, a lower percentage (64%) is observed in the ovaries. The strain is apparently unaffected despite this massive loss of genes, coding for four tRNA and for complex I and III subunits. Contrary to observations of similar situations in man, the mutant strain shows no accumulation or structurally abnormal mitochondria. Furthermore, cytochemical studies fail to detect mitochondria devoid of cytochrome oxidase activity (COX-). Finally, mitoribosome populations are identical in mitochondria from both strains. These results suggest that, in the mutant strain, there are no mitochondria containing deleted genomes only: heteroplasmy would thus be intramitochondrial.

In the studied mutant strain of Drosophila subobscura, 78% of the mitochondrial genomes lost >30% of the coding region by deletion. The mutations was genetically stable. Despite this massive loss of mitochondrial genes, the mutant did not seem to be affected. Distribution of the two genome types, cell levels of mitochondrial DNA, steady-state concentrations of the mitochondrial gene transcripts, mitochondrial enzymatic activities, and ATP synthesis capacities were measured in the head, thorax, and abdomen fractions of the mutant strain in comparison with a wild type strain. Results indicate that the deleted genomes are detected in all fractions but to a lesser extent in the male and female abdomen. In all fractions, there is a 50% increase in cellular mitochondrial DNA content. Although there is a decrease in steady-state concentrations of mitochondrial transcripts of genes affected by deletion, this is smaller than expected. The variations in mitochondrial biochemical activities in the different fractions of the wild strain are upheld in the mutant strain. Activity of complex I (involved in mutation) nevertheless shows a decrease in all fractions; activity of complex III (likewise involved) shows little or no change; finally, mitochondrial ATP synthesis capacity is identical to that observed in the wild strain. This latter finding possibly accounts for the lack of phenotype. This mutant is a good model for studying mitochondrial genome alterations and the role of the nuclear genome in these phenomena.Various alterations in the mitochondrial genome have been correlated with severe human pathology (1-3). Among the most substantial of these alterations, deletions, which account for a small fraction of the described cases, have always been detected at the heteroplasmic state (4 -6). Once the proportion of deleted genomes reaches a critical threshold, these deletions have often very pejorative effects on mitochondrial function (7,8). Such mutations are generally sporadic, although dominant autosomal factors have been observed (9 -11). A locus has been localized on chromosome 10, but no gene has yet been identified.In the heteroplasmic state, the mutant Drosophila subobscura strain studied in our laboratory presents a substantial mtDNA 1 deletion (30% of the coding region) (12). Contrary to clinical findings (1), this mutation remains stable from one generation to the next. It does not seem to affect the mutant (apparent absence of phenotype) in terms of reproduction (number of embryos, emergence of larvae), life span, or flight capacities. This strain thus offers a good model for studying possible biochemical and molecular consequences of severe mitochondrial genome alteration and the responses that enable the mutant to survive.The first investigations, performed in the whole adult fly (13), showed a strong heteroplasmic tendency in the deleted molecules; this affected 78% of the mitochondrial genomes. mtDNA cell content (per nuclear genome) showed a 50% increase in the mutant strain compared with the D. subobscura ...

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