The yeast gene, ACPI, encoding the mitochondrial acyl carrier protein, was deleted by gene replacement. The resulting acpl-deficient mutants had only 5-10% of the wild-type lipoic acid content remaining, and exhibited a respiratorydeficient phenotype. Upon meiosis, the lipoate deficiency cosegregated with the acpl deletion. The role of ACPI in longchain fatty acid synthesis was studied in fasl and fas2 null mutants completely lacking cytoplasmic fatty acid synthase. When grown on odd-chain (13:0 and 15:0) fatty acids, these cells showed less than 1% of C-16 and C-18 acids in their total lipids. Mitochondrial ACP is therefore suggested to be involved with the biosynthesis of octanoate, a precurser to lipoic acid.
Mutations in either the Drosophila melanogaster pelota or pelo gene or the Saccharomyces cerevisiae homologous gene, DOM34, cause defects of spermatogenesis and oogenesis in Drosophila, and delay of growth and failure of sporulation in yeast. These phenotypes suggest that pelota is required for normal progression of the mitotic and meiotic cell cycle. To determine the role of the pelota in mouse development and progression of cell cycle, we have established a targeted disruption of the mouse Pelo. Heterozygous animals are variable and fertile. Genotyping of the progeny of heterozygous intercrosses shows the absence of Pelo ؊/؊ pups and suggests an embryo-lethal phenotype. Histological analyses reveal that the homozygous Pelo deficient embryos fail to develop past day 7.5 of embryogenesis (E7.5). The failure of mitotic active inner cell mass of the Pelo ؊/؊ blastocysts to expand in growth after 4 days in culture and the survival of mitotic inactive trophoplast indicate that the lethality of Pelo-null embryos is due to defects in cell proliferation. Analysis of the cellular DNA content reveals the significant increase of aneuploid cells in Pelo ؊/؊ embryos at E7.5. Therefore, the percent increase of aneuploid cells at E7.5 may be directly responsible for the arrested development and suggests that Pelo is required for the maintenance of genomic stability.The Pelo gene was originally identified in a mutagenesis screen for spermatogenesis-specific genes of Drosophila melanogaster (7). Spermatogenesis in pelo mutants progresses normally during the four mitotic divisions, and the 16 spermatocytes undergo a premeiotic S-phase and duplicate their DNA content. However, spermatocytes in the mutant arrested prior to full chromosome condensation, spindle pole organization, and nuclear breakdown. Metaphase and anaphase figures of the meiotic divisions, which are clearly recognized in squashed preparations of wild-type testis, were not observed in testis of the pelo mutant. Although meiotic division arrests in pelo spermatocytes, germ cell differentiation continues, resulting in 4N spermatids with head and tail structures. These results indicate that the Pelo is required for the meiotic division during the G 2 /M transition (10). Beside the effect of the mutation on spermatogenesis, the eyes of the pelo homozygotes are up to 30% smaller than those of wild-type siblings, and the ovaries in mutants are very small. In contrast to the arrest in meiotic divisions in male germ cells, during oogenesis the mitotic divisions are affected. The mitotic zone of ovaries appears disorganized and often contains degenerating cells. Despite the apparent phenotype observed in the gametogenesis of Drosophila mutant, the pelo transcripts are not restricted to germ cells but also detected in early embryonic development.Analysis of mitotic and meiotic division in the dom34 mutant of Saccharomyces cerevisiae, which has a mutation in the pelota orthologous gene, reveals that the dom34 mutant exhibits a growth delay and fails to undergo sporulation pr...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.