酿酒酵母非发酵代谢调控
2007-06-17 14:48:04   来源：网络数据库   评论：0 点击：

the R box target genes is constitutive. Thus, Rtg2 is dispensable for retrograde gene activation in the absence of Mks1. Rtg2 and Mks1 physically interact and Mks1 is a phosphoprotein whose phosphorylation pattern resembles that of Rtg3 (Sekito et al. 2002). Recently, Rtg2 was also identified as a subunit of the SAGA-related transcriptional coactivator and histone acetyltransferase complex SLIK (Pray-Grant et al. 2002), indicating that at least some Rtg2 must also be present in the nucleus.

An additional negative regulator of RTG-dependent gene expression is encoded by the essential LST8 gene (Liu et al. 2001). Some mutations in LST8 suppress a rtg2 null mutation and alleviate glutamate repression of R box-driven genes. However, the molecular function of Lst8, which contains seven WD40 repeats possibly involved in protein–protein interactions, is only poorly understood. Signaling upstream and downstream of Rtg2 may be affected. In conclusion, retrograde control, which was originally identified as a particular pathway of communication between mitochondria and the nucleus, is now considered as a link for coordinating carbon and nitrogen metabolism.

Regulation of glyoxylate cycle and gluconeogenesis
Uptake of substrates and patterns of gene regulation
Growth of S. cerevisiae with a nonfermentable substrate such as glycerol, lactate, ethanol or acetate requires its oxidative breakdown (generation of energy) and the formation of sugar phosphates and other carbon metabolites (generation of biomass). Thus, genes of respiratory enzymes and genes of gluconeogenesis show a considerable co-regulation (DeRisi et al. 1997), although distinct regulatory DNA motifs and transcriptional activators are involved.

Glycerol can be utilized as a carbon substrate but also has an important role for osmoregulation (reviewed by Hohmann 2002). Glycerol is transported into the cell by a proton symport mechanism, requiring the GUP1 (and possibly the related GUP2) gene product (Holst et al.2000).Mutants with defects in glycerol utilization allowed the isolation of genes GUT1 (Pavlik et al. 1993) and GUT2 (Ronnow and Kielland-Brandt 1993), encoding a cytoplasmic glycerol kinase and a mitochondrial FADdependent glycerol-3-phosphate dehydrogenase, respectively. As a result of both enzyme activities, glycerol is converted into DHAP, which subsequently enters the glycolytic or gluconeogenic pathway. GUT1 and GUT2 are both transcriptionally regulated by the carbon source, although distinct activators may be involved. While GUT1 requires Adr1 (an alcohol dehydrogenase regulator; see below) for maximal expression (Pavlik et al. 1993), the GUT2 promoter contains a CCAAT box bound by Hap2–Hap5 (Grauslund and Ronnow 2000). Activation of the glycerol-3-phosphate dehydrogenase geneGUT2by Hap2–Hap5 makes sense, since this enzyme also contributes to the transfer of cytoplasmic redox equivalents to mitochondrial NAD (reviewed by Bakker et al. 2001). Interestingly, GUT1 is also regulated by an inositol/choline responsive element-activating element and its binding factor Ino2/Ino4, emphasizing the importance of glycerol-3-phosphate for phospholipid biosynthesis (Schu¨ ller et al. 1995; Grauslund et al. 1999)

The initial step of lactate catabolism is its uptake by a proton symport mechanism, executed by the Jen1 permease (Casal et al. 1999), which is also able to transport pyruvate (Makuc et al. 2001). Oxidation of D-lactate or L-lactate to give pyruvate requires the mitochondrial lactate cytochrome c oxidoreductases (L-LCR or D-LCR) encoded by CYB2 (Guiard 1985) or DLD1 (Lodi and Ferrero 1993), respectively. Both reductase genes show oxygen-dependent activation by Hap1 and carbon source regulation by Hap2–Hap5 (Lodi and Guiard 1991; Lodi et al. 1999; Ramil et al. 2000), which also affects JEN1 (Lodi et al. 2002). Besides co-regulation with respiratory genes, lactate metabolism is controlled by the gluconeogenic activators Adr1 (CYB2; Ramil et al. 2000) and Cat8 (JEN1; Bojunga and Entian 1999). Similar to what was found for SDH2, the half-life of the JEN1 transcript was substantially reduced following a shift from lactate- to glucose-containing media, supporting the view of a glucose-induced mechanism of mRNA degradation (Andrade and Casal 2001).

Although uptake of ethanol and acetate may occur by passive diffusion, evidence for the existence of at least an acetate carrier has been obtained (Casal et al. 1996). Possibly, this permease is affected in ace8 mutants which grow with ethanol but not with acetate (Paiva et al. 1999). However, the corresponding gene has not yet been described. Metabolic conversion of ethanol or acetate into glucose-6-phosphate can be divided into three separate pathways (production of acetyl-CoA, production of oxaloacetate by the glyoxylate cycle, gluconeogenesis; Fig. 1) which nevertheless are transcriptionally co-regulated. After