No abstract

Mitochondrial mass and activity must be adapted to tissue function, cellular growth and nutrient availability. In mammals, the related transcriptional coactivators PGC-1alpha, PGC-1beta and PRC regulate multiple metabolic functions, including mitochondrial biogenesis. However, we know relatively little about their respective roles in vivo. Here we show that the Drosophila PGC-1 family homologue, Spargel, is required for the expression of multiple genes encoding mitochondrial proteins. Accordingly, spargel mutants showed mitochondrial respiration defects when complex II of the electron transport chain was stimulated. Spargel, however, was not limiting for mitochondrial mass, but functioned in this respect redundantly with Delg, the fly NRF-2alpha/GABPalpha homologue. More importantly, in the larval fat body, Spargel mediated mitochondrial activity, cell growth and transcription of target genes in response to insulin signalling. In this process, Spargel functioned in parallel to the insulin-responsive transcription factor, dFoxo, and provided a negative feedback loop to fine-tune insulin signalling. Taken together, our data place Spargel at a nodal point for the integration of mitochondrial activity to tissue and organismal metabolism and growth.

No abstract

Structural maintenance of chromosomes (SMC) proteins interact with DNA in chromosome condensation, sister chromatid cohesion, DNA recombination, and gene dosage compensation. How individual SMC proteins and their functional domains bind DNA has not been described. We demonstrate the ability of the Cterminal domains of Saccharomyces cerevisiae SMC1 and SMC2 proteins, representing two major subfamilies with different functions, to bind DNA in an ATP-independent manner. Three levels of DNA binding specificity were observed: 1) a >100-fold preference for doublestranded versus single-stranded DNA; 2) a high affinity for DNA fragments able to form secondary structures and for synthetic cruciform DNA molecules; and 3) a strong preference for AT-rich DNA fragments of particular types. These include fragments from the scaffoldassociated regions, and an alternating poly(dA-dT)-poly(dT-dA) synthetic polymer, as opposed to a variety of other polymers. Reannealing of complementary DNA strands is also promoted primarily by the C-terminal domains. Consistent with their in vitro DNA binding activity, we show that overexpression of the SMC C termini increases plasmid loss without altering viability or cell cycle progression.The structural maintenance of chromosomes (SMC) 1 protein family, with members from lower and higher eukaryotes, may be divided into four subfamilies (SMC1 to SMC4) and two SMC-like protein subfamilies (SMC5 and SMC6) (for reviews see Refs. 1-7). Members of this family appear to function primarily as heterodimers and are implicated in a large range of activities that modulate chromosome structure and organization. Studies of yeast strains deficient in SMC1 and SMC2 show defects in the segregation of mitotic chromosomes (8 -10). A role in chromosome condensation was demonstrated in a cell-free chromosome condensation assay based on Xenopus laevis oocyte extracts (11), in which SMC2 and SMC4 subtypes were identified as essential components of the condensin protein complex (12). More recently, the Smc1p and Smc3p of Saccharomyces cerevisiae were shown to be essential for sister chromatid cohesion (13,14), and in Caenorhabditis elegans, two SMC protein homologs, MIX-1 and DPY-27, are involved in gene dosage compensation (15, 16). Finally, evidence for a role of SMC proteins in DNA recombination and repair has been supported by both genetic and biochemical studies. The Schizosaccharomyces pombe Rad18 gene and its S. cerevisiae homolog RHC18 are SMC-like and were found to act in an unusual postreplicative recombinational repair pathway (17), whereas mammalian SMC1 and SMC3 proteins were described as essential subunits of a recombinational repair protein complex (RC-1), isolated from calf thymus (18,19).SMC proteins display a very characteristic structure: two coiled-coil domains separate evolutionarily conserved head and tail domains, which contain an NTP binding motif (Walker A box) in the N terminus, and a DA box (Walker B) in the C terminus (20). The similarity of SMC proteins to motor proteins such as kinesin a...

The Drosophila cyclin-dependent protein kinase complex Cyclin D/Cdk4 induces cell growth (accumulation of mass) as well as proliferation (cell cycle progression). To understand how CycD/Cdk4 promotes growth, we performed a screen for modifiers of CycD/Cdk4-driven overgrowth in the eye. Loss-of-function mutations in Hif-1 prolyl hydroxylase (Hph), an enzyme involved in the cellular response to hypoxic stress, dominantly suppress the growth but not the proliferation function of CycD/Cdk4. hph mutant cells are defective for growth, and, remarkably, ectopic expression of Hph is sufficient to increase cellular growth. Epistasis analysis places Hph downstream of CycD/Cdk4. Overexpressed CycD/Cdk4 causes an increase in Hph protein in tissues where Hph induces growth, suggesting a mechanism whereby Hph levels are regulated posttranscriptionally in response to CycD/Cdk4. Our data suggest that Hph, in addition to its function in hypoxic response, is a regulator of cellular growth and that it is a key mediator for CycD/Cdk4.

The information from preoperative cross-sectional spiral tomography has minor impact on treatment planning in standard implant cases in mandibular premolar and molar regions. The clinical examination provides sufficient information for selecting implant diameter and the panoramic radiograph provides sufficient information for implant length selection.

No abstract

No abstract