Glutamate Interacts with VDAC and Modulates Opening of the Mitochondrial Permeability Transition Pore

The amino acid glutamate, synthesized in the mitochondria, serves multiple functions, including acting as a neurotransmitter and participating in degradative and synthetic pathways. We have previously shown that glutamate modulates the channel activity of bilayer-reconstituted voltage-dependent anion channel (VDAC). In this study, we demonstrate that glutamate also modulates the opening of the mitochondrial permeability transition pore (PTP), of which VDAC is an essential component. Glutamate inhibited PTP opening, as monitored by transient Ca2+ accumulation, mitochondrial swelling and accompanying release of cytochrome c. Exposure to L-glutamate delayed the onset of PTP opening up to 3-times longer, with an IC50 of 0.5 mM. Inhibition of PTP opening by L-glutamate is highly specific, not being mimicked by D-glutamate, L-glutamine, L-aspartate, or L-asparagine. The interaction of L-glutamate with VDAC and its inhibition of VDAC's channel activity and PTP opening suggest that glutamate may also act as an intracellular messenger in the mitochondria-mediated apoptotic pathway.     

Effects of nicotine on the biosynthesis of carotenoids in halophilic Archaea (class Halobacteria): an HPLC and Raman spectroscopy study

Extremophiles - Nicotine has a profound influence on the carotenoid metabolism in halophilic Archaea of the class Halobacteria. In a study of Halobacterium salinarum, Haloarcula marismortui and...     

Reconstitution of p53 expression in a nonproducer Ab-MuLV-transformed cell line by transfection of a functional p53 gene

L12 are Ab-MuLV-transformed cells that express the abl p120 oncogene product but lack the cellularly encoded p53. The functional p53 gene in these cells has been inactivated by the insertion of Moloney virus-like sequences into the first p53 intron. Transfection of L12 cells with a functional p53 gene, contained in a 16 kb Eco RI genomic cloned fragment gave rise to L12-derived cell lines with novel p53 sequences of various sizes and copy number. A high percentage of L12-derived clones efficiently transcribed p53 mRNA and synthesized the p53 protein. Whereas injection of L12 parental cells into syngeneic mice caused the development of local tumors that later regressed, L12-derived clones that expressed p53 caused lethal tumors in syngeneic mice, thus behaving similarly to other Ab-MuLV-transformed p53-producer cell lines. These results suggest that the expression of p53 is essential for tumor cells to exhibit a fully transformed phenotype, manifested in lethal tumors in syngeneic mice.     

Initiation of meiosis in cell cycle initiation mutants of Saccharomyces cerevisiae

Control of the initiation of meiosis in yeast was examined in diploids homozygous for one of four different temperature-sensitive mutations that affect “start” of the mitotic cell cycle. Two of the mutations, cdc28 and tra3, bring about deficiencies in the initiation of meiosis, while cdc25 and cdc35 do not prevent initiation of normal meiosis at both permissive and restrictive temperatures. Moreover, diploids homozygous for the latter two mutations are capable of initiating meiosis in rich growth media upon transfer to the high, non-permissive temperature. This unique feature contrasts with the behavior of other yeast strains which require a starvation sporulation medium for initiation of meiosis. It is suggested that the initiation of meiosis includes functions that are shared with “start” of the mitotic cell cycle, as well as functions related to the choice between the two processes. Meiosis in vegetative media at the restrictive temperature (in cdc25 or cdc35 homozygotes) may be important for the study of chemical and physiological phenomena resulting from the meiotic process and not from adaptation to the sporulation medium.