Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death

Opposing mitochondrial fission and fusion reactions determine the shape and interconnectivity of mitochondria. Dynamin-related protein 1 (Drp1) is an ancient mechanoenzyme that uses GTP hydrolysis to power the constriction and division of mitochondria. Although Drp1-mediated mitochondrial fragmentation is recognized as an early event in the apoptotic programme, acute regulation of Drp1 activity is poorly understood. Here, we identify a crucial phosphorylation site that is conserved in all metazoan Drp1 orthologues. Ser 656 is phosphorylated by cyclic AMP-dependent protein kinase and dephosphorylated by calcineurin, and its phosphorylation state is controlled by sympathetic tone, calcium levels and cell viability. Pseudophosphorylation of Drp1 by mutation of Ser 656 to aspartic acid leads to the elongation of mitochondria and confers resistance to various pro-apoptotic insults. Conversely, the constitutively dephosphorylated Ser656Ala mutant Drp1 promotes mitochondrial fragmentation and increases cell vulnerability. Thus, Drp1 phosphorylation at Ser 656 provides a mechanism for the integration of cAMP and calcium signals in the control of mitochondrial shape, apoptosis and other aspects of mitochondrial function.     

Structure determinants and substrate recognition of serine carboxypeptidase-like acyltransferases from plant secondary metabolism

Structures of the serine carboxypeptidase-like enzymes 1-O-sinapoyl-beta-glucose:L-malate sinapoyltransferase (SMT) and 1-O-sinapoyl-beta-glucose:choline sinapoyltransferase (SCT) were modeled to gain insight into determinants of specificity and substrate recognition. The structures reveal the alpha/beta-hydrolase fold as scaffold for the catalytic triad Ser-His-Asp. The recombinant mutants of SMT Ser173Ala and His411Ala were inactive, whereas Asp358Ala displayed residual activity of 20%. 1-O-sinapoyl-beta-glucose recognition is mediated by a network of hydrogen bonds. The glucose moiety is recognized by a hydrogen bond network including Trp71, Asn73, Glu87 and Asp172. The conserved Asp172 at the sequence position preceding the catalytic serine meets sterical requirements for the glucose moiety. The mutant Asn73Ala with a residual activity of 13% underscores the importance of the intact hydrogen bond network. Arg322 is of key importance by hydrogen bonding of 1-O-sinapoyl-beta-glucose and L-malate. By conformational change, Arg322 transfers L-malate to a position favoring its activation by His411. Accordingly, the mutant Arg322Glu showed 1% residual activity. Glu215 and Arg219 establish hydrogen bonds with the sinapoyl moiety. The backbone amide hydrogens of Gly75 and Tyr174 were shown to form the oxyanion hole, stabilizing the transition state. SCT reveals also the catalytic triad and a hydrogen bond network for 1-O-sinapoyl-beta-glucose recognition, but Glu274, Glu447, Thr445 and Cys281 are crucial for positioning of choline.     

3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors

A series of 3-aryl-4-hydroxyquinolin-2(1H)-ones with fatty acid synthase inhibitory activity was prepared. Starting from a derivative with an IC(50) = 1.4 microM, SAR studies led to compounds with more than 70-fold increase in potency (IC(50) < 20 nM).     

Wege zur Endomykorrhiza. Einladung ans Buffet

The ancient arbuscular mycorrhiza represents a mutualistic symbiotic interaction of plants with soil‐born fungi. The fungus assists the plant in requiring mineral nutrients and water, whereas the plant supplies the biotrophic fungus with carbohydrates. This interaction is widespread and enables the plant to cope with unfavourable conditions (e.g. limited nutrient supply as well as drought, salt and heavy metal stress or pathogen attack). This review describes the state of the art concerning the establishment and regulation of the plant‐fungus interaction. Early signals leading to a successful colonization and the following mechanisms of the plant to host the fungus are explained. Another focus is given on the regulation of the transfer of carbohydrates to the fungus, the restriction of fungal growth by autoregulative mechanisms and the function of phytohormones, all part of a plant regulatory machinery that is necessary to ensure a functional and balanced symbiosis.     

Die facettenreiche Welt der Apocarotinoide. Farben,Düfte,Aromen und Hormone

Apocarotenoids are tailored from carotenoids by highly specific oxidative enzymes cleaving different double bonds. New chromophores can be generated, which make additional nuances of the yellow‐red color spectrum available. Colorless C13 apocarotenoids can constitute potent scent and aroma compounds. Many apocarotenoid hormone functions are well‐known (abscisic acid in plants, trisporic acid in fungi, retinoic acid in mammals). A new class of apocarotenoid plant hormones, which take part in determining shoot branching has recently been identified as strigolactones. In the biosyntheses of strigolactones and mycorrhiza‐induced C13/C14 apocarotenoids several sequential cleavage reactions occur. The knowledge about biosynthetic pathways and functions of apocarotenoids opens up new perspectives for its application in horticulture and in the control of parasitic weeds as well as in the manipulation of flower scents and fruit aromas.     

Organic matter accumulation in a restored peatland: Evaluating restoration success

Recent advances in peatland restoration techniques have succeeded in establishing Sphagnum moss on the remnant cutover peat surface following peat extraction; however, evaluating restoration success remains a key issue. We argue that a Sphagnum-dominated peatland can only be considered functionally ‘restored’ once organic matter accumulation has achieved a thickness where the mean water table position in a drought year does not extend into the underlying formerly cutover peat surface. Here we monitor the spatio-temporal development of organic matter accumulation in a new peat layer for the first 8 years following the restoration of a Québec peatland and couple a simple acrotelm carbon accumulation model and ecohydrological model to assess peatland restoration success.We determined that organic matter accumulation increased from 2.3 ± 1.7 cm 4 years post-restoration to 13.6 ± 6.5 cm 8 years post-restoration. For comparison, at an adjacent non-restored section of the peatland organic matter accumulation was significantly lower (p < 0.001 for all years), with mean thicknesses of 0.2 ± 0.6 and 0.8 ± 1.2 cm for 24 and 28 years post-extraction, respectively. Given the mean summer water deficit at the site (?64 mm), our ecohydrological modeling results suggest that a 19-cm-thick moss layer would be required to offset the water table decrease induced by the summer water deficit. Given the current rate of organic matter accumulation, net primary productivity and the new peat layer decomposition rates determined using litter bags, we estimate it will take 17 years post-restoration to accumulate a 19-cm moss layer. Consequently, we argue that successful peatland restoration may be achieved in the medium-term and that our simple modeling approach can be useful in assessing the long-term impact of restoration on atmospheric carbon dioxide sequestration.