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[en] Highlights: • Mitochondrial ultrastructure defines (patho)physiology. • Description of morphometric parameters to define cristae shape. • Dissection of OPA1, MICOS and ATPase dimers contribution in the modulation of mitochondrial ultrastructure. Mitochondrial adaptation to different physiological conditions highly relies on the regulation of mitochondrial ultrastructure, particularly at the level of cristae compartment. Cristae represent the membrane hub where most of the respiratory complexes embed to account for OXPHOS and energy production in the form of adenosine triphosphate (ATP). Changes in cristae number and shape define the respiratory capacity as well as cell viability. The identification of key regulators of cristae morphology and the understanding of their contribution to the mitochondrial ultrastructure and function have become an strategic goal to understand mitochondrial disorders and to exploit as therapeutic targets. This review summarizes the known regulators of cristae ultrastructure and discusses their contribution and implications for mitochondrial dysfunction.

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[en] The crystal structure of adenosine, C₁₀H₁₃N₅O₄, M_r=267.24, has been refined by full-matrix least-squares methods using single-crystal neutron diffraction data (sinθ/λ<0.79 A^-1) measured at 123 K. (orig./WL)

[en] Perturbation of hematopoiesis is a life-threatening consequence of an exposure to ionizing radiation in situations of nuclear accidents, contingent terrorist attacks, or possible war using nuclear weapons. Search for drugs which would alleviate radiation-induced myelosuppression is a long term task for laboratories focusing their activities on pharmacological modulation of radiation damage. The hypothesis about contingent stimulatory effects of pharmacological activation of adenosine membrane receptors on radiation-suppressed hematopoiesis has been originally postulated in the laboratory of the authors. Beneficial effects of drugs elevating extracellular adenosine, i.e. of a combination of adenosine monophosphate, an adenosine prodrug, and dipyridamole, which prevents the cellular uptake of adenosine, have been found when the drugs were administered either before or after irradiation with a single dose, as well as when given repeatedly in the course of repeated irradiation. Elevated extracellular adenosine has been also observed to potentiate hematopoiesis-stimulating effects of granulocyte colony-stimulating factor. Recently attention of the authors has been focused on testing the hematopoiesis-modulating effects of synthetic agonists of adenosine receptors, more or less selective for individual adenosine receptor subtypes. Whereas the agonist of adenosine A1 receptors, CPA, has been found to suppress the proliferation of hematopoietic progenitor and precursor cells, the adenosine A3 receptor agonist, IB-MECA, has been observed to possess significant pro-stimulatory activity. These results strongly suggest that pharmacological activation of adenosine membrane receptors might find its use in the treatment of radiation-induced myelosuppression. (author)

[en] A correlation between high-performance liquid chromatography (HPLC) analysis and an in situ enzyme-linked immunosorbent assay (ELISA) for 8,5'-cycloadenosine formation in irradiated poly(A) has been established. The correlation shows that the ELISA precisely reflects changes in the combined yield of R- and S-8,5'-cycloadenosine but that a correction factor must be applied to the ELISA values for accuracy. The HPLC analysis reveals that the intramolecular cyclization proceeds stereoselectively in irradiated poly(A) to preferentially produce the R isomer at pH 7.0 which is similar to the result for irradiated adenosine but in contrast to the result for 5'-AMP where the S isomer predominates at neutral pH. The HPLC analysis shows that two events originating in hydroxyl radical attack at the sugar phosphate backbone in poly(A); that is, adenine release and 8,5'-cycloadenosine formation have somewhat different dose-yield responses. The formation of 8-hydroxyadenosine was detected in the HPLC chromatograms of poly(A) irradiated under N2O at neutral pH, and the yield of this compound was similar to the yield observed in 5'-AMP or adenosine irradiated under similar conditions

[en] Our trial for 8-alkylation of adenosine derivatives showed excellent results in methylation reaction under mild reaction condition, but only moderate results for ethylation. Although, the reaction scope is somewhat limited, this high yielding and yet very convenient methodology to secure valuable key intermediates and starting from the large stock of compounds 1 and 2 would expedite to prepare our dream compounds c-ADPR containing azido group at sugar portion and alkyl group at 8-position of purine base. The modification at 8-position of purine moiety is of particular interest, since it could influence strongly syn/anti conformation of the purine base, which could in turn cause significant changes in the interaction between the substrate molecules and active sites of enzymes or receptors. In addition, the introduction of alkyl substituents to purine could afford the desired lipophilicity for cell permeability to adenosine-containing biomolecules such as cyclic-adenosine diphosphoribose (cADPR) and β-NAD⁺. In our ongoing synthetic efforts to prepare structurally diverse adenosine-containing biomolecules such as cADPR, and enzyme inhibitors against adenosyl-L-homocysteine hydrolase, our work has been extended to the syntheses of both purine- and sugar-modified adenosine derivatives as another potential synthetic intermediates. In the precedent work, we reported the convenient synthetic route to prepare sugar-modified adenosine derivatives having an azido group and their reductive products at 2' or 3'-position of ribose moiety.