A site-specific deletion in mitochondrial DNA of Podospora is under the control of nuclear genes.

Abstract

In the filamentous fungus Podospora anserina, the association of two nuclear genes inevitably leads to a "premature death" phenotype consisting of an early end of vegetative growth a few days after ascospore germination. Mycelia showing this phenotype contain a mitochondrial chromosome that always bears the same deletion. One of the break points is exactly at the 5' splice site of a particular mitochondrial intron, suggesting that the deletion event could result from molecular mechanisms also involved in intron mobility.One of the nuclear genes involved in triggering this site-specific event belongs to the mating-type minus haplotype; the other is a mutant allele of a gene encoding a cytosolic ribosomal protein.In obligate aerobes, rearrangements of mitochondrial DNA (mtDNA) are responsible for various deleterious symptoms, such as maternally inherited male sterility in plants (1), several mycelial degenerative phenomena in fungi (2), and, as described more recently in humans, numerous neuromuscular (3) or hematological (4) diseases. In some cases, nuclear genes have been shown to control the mtDNA rearrangements (5, 6). The molecular mechanisms producing these rearrangements and the role played by nuclear-encoded proteins remain unclear in all cases.In the filamentous fungus Podospora anserina, vegetative growth is limited by a maternally inherited syndrome, called senescence, ending in cessation of mycelial elongation and apical cell death (7,8). In this species, senescence is clearly associated with mtDNA rearrangements and most probably is caused by them. More precisely, it has been shown that short mtDNA sequences are amplified as circular multimeric DNA molecules in senescent cultures (9)(10)(11)(12)(13)(14). It was shown that the most frequently amplified sequence corresponds exactly to a mitochondrial intron (15), intron a, and that most of the mutations allowing mycelia to escape senescence are rearrangements in intron a (12,(16)(17)(18). It has been known for a long time (19) that the nuclear genome controls the life-span of the fungus. For instance, the life-span of our reference strains differs according to their mating type: the process of senescence is delayed in mat+ strains compared with matones. However the differences, although significant, are not striking (see Table 1). Moreover the functions encoded by these genes are still unknown.The work presented here follows the observation that, in Podospora, mutations in several genes involved in the control of translational accuracy have an effect on the life-span (A. Raynal, personal communication; Table 1). As a first step, we focused our attention on the AS1-4 mutation. This particular allele confers a very long life-span to mat+ mycelia, while, when associated with mat-, it leads systematically to the premature death phenotype, consisting of an early end of mycelial growth a few days after ascospore germination.We showed that mycelia presenting this phenotype were in all cases heteroplasmic and that they systematically contained the same ...

Biochemical and Molecular Consequences of Massive Mitochondrial Gene Loss in Different Tissues of a Mutant Strain of Drosophila subobscura

“…Electron microscopy indicates no structural mitochondrial anomalies, and all mitochondria show a cytochrome oxidase activity for any type of tissue (15). This mutant thus survives substantial alterations to most of its mitochondrial genomes, a phenomenon that gives rise to severe pathological consequences in man or has been correlated with premature death in Podospora anserina (32,33).…”

Mutations at the Arabidopsis CHM locus promote rearrangements of the mitochondrial genome.

“…Nuclear mutations that promote elevated rates of plastid mutations have been reported in petunia (Potrykus, 1970), Oenothera (Epp, 1973;Chiu et al, 1990), and maize (Thompson et al, 1983). Nuclear genes that control mitochondrial rearrangements are known in humans (Zeviani et al, 1989) and fungi (SeideCRogol et al, 1989;Belcour et al, 1991). In plants, there is evidence that the nuclear genetic background affects the frequency of mitochondrial genome rearrangements (Laughnan and GabayLaughnan, 1983;Newton and Coe, 1986), and at least one nuclear gene has been identified that is responsible for the loss of specific DNA sequences from the mitochondrial genome (Mackenzie and Bassett, 1987;Mackenzie and Chase, 1990).…”

Maintaining Two Mating Types: Structure of the Mating Type Locus and Its Role in Heterokaryosis inPodospora anserina

“…It is known from previous studies that phenotypic differences exist between the S mat+ and S mat2 mycelia of P. anserina S strain. For example, S mat+ and S mat2 grow at the same rate as S mat+/mat2, yet the S mat2 strain presents a shorter life span than the S mat+ strain (Marcou 1961), a differential suppression of the su8-1 suppressor tRNA (Silar et al 2000), triggers the "premature death" syndrome more frequently (Belcour et al 1991) and is slightly more thermoresistant (Contamine et al 2004). More recently, genome-wide microarray analysis revealed that many genes are differentially transcribed in S mat+ and S mat2 strains (Bidard et al 2011).…”