During the past years, yeasts have been successfully established as models to study the mechanisms of apoptotic regulation. We recently showed that mutations in the LSM4 gene, which is involved in messenger RNA decapping, lead to increased mRNA stability and apoptosis in yeast. Here, we show that mitochondrial function and YCA1, which encodes a budding yeast metacaspase, are necessary for apoptosis triggered by stabilization of mRNAs. Deletion of YCA1 in yeast cells mutated in the LSM4 gene prevents mitochondrial fragmentation and rapid cell death during chronological ageing of the culture, diminishes reactive oxygen species accumulation and DNA breakage, and increases resistance to H 2 O 2 and acetic acid. mRNA levels in lsm4 mutants deleted for YCA1 are still increased, positioning the Yca1 budding yeast caspase as a downstream executor of cell death induced by mRNA perturbations. In addition, we show that mitochondrial function is necessary for fast death during chronological ageing, as well as in LSM4 mutated and wild-type cells.
Damaging environment, certain intracellular defects or heterologous expression of pro-apoptotic genes induce death in yeast cells exhibiting typical markers of apoptosis. In mammals, apoptosis can be directed by the activation of groups of proteases, called caspases, that cleave specific substrates and trigger cell death. In addition, in plants, fungi, Dictyostelium and metazoa, paracaspases and metacaspases have been identified that share some homologies with caspases but showing different substrate specificity. In the yeast Saccharomyces cerevisiae, a gene (MCA1/YCA1) has been identified coding for a metacaspase involved in the induction of cell death. Metacaspases are not biochemical, but sequence and functional homologes of caspases, as deletion of them rescues entirely different death scenarios. In this review we will summarize the current knowledge in S. cerevisiae on apoptotic processes, induced by internal and external triggers, which are dependent on the metacaspase gene YCA1.
Over the last twenty years, progress in diagnosis and in adjuvant therapy in the field of malignant bone tumor treatment has allowed for development of limb-saving surgical techniques after oncological excision. In this context, the use of vascularized fibula for transplantation represents an important instrument in the reconstruction of bone, either with or without allografts.Moreover, in pediatric cases, the vascularized transplant of the proximal fibula with its open physis allows for an adequate reconstruction of the bone loss and the possibility of conserving the growth potential of the segment. The purpose of this article is to illustrate the various reconstructive possibilities that the use of the combined graft technique (VFT plus allograft) offers in the treatment of large-scale bone loss. In our department from 1988 to 2000, 142 vascularized fibula transplants were performed in oncological cases. Surgical reconstruction was carried out on the tibia in 70 cases, on the femur in 40, on the humerus in 26 and on the radius in 6. Combined graft intercalary reconstructions were 92. In 22 pediatric cases the fibula was transplanted, including the proximal growing epiphysis in the graft; in two of these cases massive allograft was associated to the VFG. Because of its biological properties, the grafted vascularized fibula allowed for fast bone fusion at the level of the osteotomy. It has also demonstrated a tendency of progressive hypertrophy and osteointegration with the allograft, when used. In 22 pediatric cases, the fibula graft with the proximal epiphysis maintained its ability to grow. Unsuccessful outcomes caused by vascular, mechanical, or septic failure were equal to 8.2 %. The fibula graft in the reconstruction of bone loss secondary to oncological excision is a trustworthy and versatile technique.
The lactose-utilizing yeast Kluyveromyces lactis is an essentially aerobic organism in which both respiration and fermentation can coexist depending on the sugar concentration. Despite a low fermentative capacity as compared to Saccharomyces cerevisiae, four structural genes encoding alcohol dehydrogenase (ADH) activities are present in this yeast. Two of these activities, namely K1ADH III and K1ADH IV, are located within mitochondria and their presence is dependent on the carbon sources in the medium. In this paper we demonstrate by transcription and activity analysis that KlADH3 is expressed in the presence of low glucose concentrations and in the presence of respiratory carbon sources other than ethanol. Indeed ethanol acts as a strong repressor of this gene. On the other hand, KlADH4 is induced by the presence of ethanol and not by other respiratory carbon sources. We also demonstrate that the presence of KLADH III and KLADH IV in K. lactis cells is dependent on glucose concentration, glucose uptake and the amount of ethanol produced. As a consequence, these activities can be used as markers for the onset of respiratory and fermentative metabolism in this yeast.
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