Towards the molecular basis for the regulation of mitochondrial dehydrogenases by calcium ions

In mammalian cells, increases in calcium concentration cause increases in oxidative phosphorylation. This effect is mediated by the activation of four mitochondrial dehydrogenases by calcium ions; FAD-glycerol 3-phosphate dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase. FAD-glycerol 3-phosphate dehydrogenase, being located on the outer surface of the inner mitochondrial membrane, is exposed to fluctuations in cytoplasmic calcium concentration. The other three enzymes are located within the mitochondrial matrix.While the kinetic properties of all of these enzymes are well characterised, the molecular basis for their regulation by calcium is not. This review uses information derived from calcium binding studies, analysis of conserved calcium binding motifs and comparison of amino acid sequences from calcium sensitive and non-sensitive enzymes to discuss how the recent cloning of several subunits from the four dehydrogenases enhances our understanding of the ways in which these enzymes bind calcium. FAD-glycerol 3-phosphate dehydrogenase binds calcium ions through a domain which is part of the polypeptide chain of the enzyme. In contrast, it is possible that the calcium sensitivity of the other dehydrogenases may involve separate calcium binding subunits.     

Genetic mapping of RP1 on 8q11-q21 in an Australian family with autosomal dominant retinitis pigmentosa reduces the critical region to 4 cM between D8S601 and D8S285

The locus (RP1) for one form of autosomal dominant retinitis pigmentosa (adRP) was mapped on chromosome 8q11-q22 between D8S589 and D8S285, which are about 8 cM apart, by linkage analysis in an extended family ascertained in the USA. We have studied a multigeneration Australian family with adRP and found close linkage without recombination between the disease locus and D8S591, D8S566, and D8S166 (Z_max = 1.137– 4.650 at θ = 0.00), all mapped in the region known to harbor RP1. Assuming that the mutation of the same gene is responsible for the disease in both families, the analysis of multiply informative meioses in the American and Australian families places the adRP locus between D8S601 and D8S285, which reduces the critical region to about 4 cM, corresponding to approximately 4 Mb, which is completely covered by a yeast artificial chromosome contig assembled recently. Received: 23 April 1996 / Accepted: 3 July 1996     

Effects of predator interactions, prey palatability and habitat structure on survival of natterjack toad Bufo calamita larvae in replicated semi-natural ponds

The significance of predation and aquatic habitat structures to the survivorship of natterjack toad Bufo calamita larvae was investigated by manipulating predator numbers and pond characteristics in a series of replicated semi-natural pools over three consecutive years Two species of fish (common carp Cyprinus carpio and perch Perca fluviatilis) increased the survival of small tadpoles severalfold by selectively consuming predatory invertebrates, but a third species of fish (rudd Scardinius erythrophthalmus) devoured tadpoles and invertebrates indiscriminately Survival of larger tadpoles later in larval development was less affected by the reduction of invertebrate predation pressure from carp and perch, probably because abiotic factors (pond desiccation and anoxia) were stronger agents of tadpole mortality In ponds of low pH (ca 4 5) there was greatly increased spawn mortality and reduced tadpole growth rates but no significant change in tadpole predation compared with circumneutral controls Neutralisation of acid ponds to pH 7 by addition of Ca(OH)₂ restored spawn viability and tadpole growth rates to control levels without affecting predation level Addition of organic nutrients stimulated tadpole growth rates significantly m ohgotrophic ponds but not sufficiently to improve survival of small larvae in the face of predation Extensive growths of macrophytes increased predator numbers up to more than twofold but effects on tadpole mortality rates differed between experiments Replacement of natural substrates by concrete basins substantially increased tadpole survival throughout development, probably because both predation by invertebrates and abiotic mortality factors were ameliorated Predation was a strong force early in natterjack tadpole development irrespective of chemical and biological conditions within ponds, but became much less important compared with abiotic factors as an agent of mortality at later tunes