Showing papers on "Mitochondrial biogenesis published in 1988"

Regulation of the mitochondrial adenine nucleotide pool size in liver: mechanism and metabolic role

Abstract: The ATP-Mg/Pi carrier in liver mitochondria can catalyze the exchange of ATP-Mg on one side of the inner membrane for Pi on the other. This mechanism allows for net uptake or release of ATP-Mg from mitochondria and thus regulates the matrix ATP + ADP + AMP pool size. In isolated mitochondria, carrier activity is stimulated by submicromolar concentrations of calcium, suggesting that calcium may regulate transport rates in vivo. Whenever the carrier is active, the direction of any net changes in the matrix adenine nucleotide pool size is determined mainly by the extent to which the prevailing ATP-Mg concentration gradient deviates from an equilibrium related to delta pH through the phosphate concentration gradient. Thus it seems that in the cell, energy status (reflected by ATP:ADP ratios in the cytoplasm and matrix) determines whether calcium-mediated hormone activation of the carrier will produce an increase or a decrease in the matrix adenine nucleotide content. Consequent variations in the absolute concentrations of ATP, ADP, and AMP in the matrix may contribute to the selective regulation of those metabolic activities in the cell that have adenine nucleotide dependent steps localized to the mitochondrial compartment (gluconeogenesis, urea synthesis, mitochondrial biogenesis, and even oxidative phosphorylation).

Identification of two factors which bind to the upstream sequences of a number of nuclear genes coding for mitochondrial proteins and to genetic elements important for cell division in yeast.

Abstract: Two abundant factors, GFI and GFII which interact with the 5' flanking regions of nuclear genes coding for proteins of the mitochondrial respiratory chain have been identified. In one case (subunit VIII of QH2: cytochrome c oxidoreductase) the binding sites for both factors overlap completely and their binding is mutually exclusive. For the other 5' regions tested the GFI and GFII binding sites do not coincide. Interestingly, binding sites for GFI and GFII are also present in or at the 3' ends of the coding regions of two genes of the PHO gene family and in DNA elements important for optimal ARS and CEN function respectively. The sites recognized by GFI conform to the consensus RTCRNNNNNNACGNR, while those recognized by GFII contain the element RTCACGTG. We speculate that GFI and GFII may play a role in different cellular processes, dependent on the context of their binding sites and that one of these processes may be the coordination of the expression of genes involved in mitochondrial biogenesis with the progress of the cell cycle.

A path from mitochondria to the yeast nucleus

Abstract: We have identified a path in yeast, from mitochondria to the nucleus, which may have a regulatory function in mitochondrial biogenesis. This path is evident as an elevated expression of a number of nuclear DNA sequences in response to specific defects in the mitochondrial genome, including the absence of mitochondrial DNA in rho 0 petites. Among those nuclear sequences preferentially expressed in certain respiratory-deficient cells are stable poly(A)+ transcripts derived from the so-called non-transcribed spacer region of the nuclear ribosomal DNA repeat, where they are most abundant in the rho 0 petite. Although the function of these unusual RNAs is unclear, the observations may reflect the presence of a mitochondrial homeostatic control system in yeast, which we suggest could function to adjust the mass of mitochondria and mitochondrial DNA in the cell in response to inequities in organelle apportionment during cell budding.

Mitochondrial chloramphenicol-resistant mutants can have deficiencies in energy metabolism.

Abstract: Three pairs of mouse CAP-R PYR-IND OLI-R mitochondrial mutants, and the corresponding CAP-S parental lines, were assayed to determine if cellular expression of these phenotypes was accompanied by changes in cellular energy metabolism: glycolysis, cellular respiration, citric acid cycle activity, and mitochondrial electron transport. Relative to its parental CAPS line, the SVT2 CAP-R mutant had no significant deficiencies in any of the pathways analyzed. In contrast, the LA9 and SVA31 CAP-R mutants showed significant reductions in cellular respiration. At the biochemical level, respiration deficiency was accompanied by derangements in mitochondrial electron transport. It was also found that the CAP-R mutants had very high levels of glycolysis when the cells were maintained in the presence of chloramphenicol. The possibility is discussed that the sequence changes in the mitochondrial large rRNA gene which determine chloramphenicol resistance can also result, at least in some cases, in reduced levels of mitochondrial biogenesis, leading to respiration deficiency. The PYR-IND and OLI-R phenotypes, which also appear to be encoded by the CAP-R mutations, may result from a compensatory increase in glycolysis-generated ATP or metabolic intermediates.

Expression of the primary biliary cirrhosis antigens in yeast: aspects of mitochondrial control.

Abstract: The mitochondria of 21 yeast strains were tested for the expression of primary biliary cirrhosis (PBC) specific antigens. The amounts of the antigens in the mitochondrial preparations varied with the strains. Genetic analysis of the strain differences in antigen expression indicated nuclear control which was complex. Those strains expressing the least amounts of antigens exhibited coagulating mitochondria in organellar preparations. Additional evidence relating expression of antigens to the physiological/structural state of mitochondria was that cells grown in the presence of the mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP), failed to produce any antigens, and that glucose repression of mitochondria suppressed antigen expression. Blockage of mitochondrial protein synthesis either throughpetite mutation or by culture in the presence of erythromycin decreased the content of antigens in the mitochondria but did not competely block antigen production. The presence of the PBC antigen in the mitochondria of these cells with nonfunctional mitochondrial synthesizing machinery further indicates that these antigens are cytoplasmically synthesized. Analysis of the pre- and postmitochondrial fractions of all homogenates confirmed that the antigens are not only cytoplasmically synthesized but also have an extramitochondrial location in cells, probably in the plasma membrane.

Mitochondrial Biogenesis: Recent Developments and Insights

Abstract: Biosynthesis of a functional mitochondrion requires the coordinate expression of genes in both mitochondrial and nuclear DNAs. In yeast, three mitochondrial genes are split and RNA splicing plays a pivotal role in their expression. The recent finding that some introns are capable of self-splicing activity in vitro has permitted analysis of the mechanisms involved in RNA catalysis and may eventually shed light on the evolution of splicing mechanisms in general. Most mitochondrial proteins are encoded by nuclear genes, synthesized in the cytoplasm and imported by the organelle. The availability of cloned genes coding for several constituent subunits of the ubiquinol-cytochrome c reductase, which are imported by mitochondria, has allowed study of selected steps in the addressing of proteins to mitochondria and their intercompartmental sorting within the organelle. Recent developments are discussed.