dictyNews Electronic Edition Volume 31, number 13 October 24, 2008 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Upon publication of your paper, please send strains and plamids to  the Dicty Stock Center. For more information see  http://dictybase.org/StockCenter/Deposit.html. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ========= Abstracts ========= Biological activities of novel derivatives of DIF-1 isolated from Dictyostelium. Haruhisa Kikuchi, Shinya Ishiko, Yoshiteru Oshima, Naomi Gokan, Kohei Hosaka, and Yuzuru Kubohara* *Gunma University IMCR, Japan. BBRC, in press The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk cell differentiation in the cellular slime mold Dictyostelium discoideum.  In addition, DIF-1 and its derivatives have been shown to possess anti-leukemic activity and glucose consumption-promoting activity in vitro in mammalian cells.  In this study, to assess the chemical structure-effect relationship of DIF-1, we synthesized 8 derivatives of DIF-1 and investigated their stalk cell-inducing activity in Dictyostelium cells and pharmacological activities in mammalian cells.  Of the derivatives, two amide derivatives of DIF-1, whose hydrophobic indexes are close to that of DIF-1, induced stalk cell differentiation as strongly as DIF-1 in Dictyostelium cells.  It was also found that some derivatives suppressed cell growth in human K562 leukemia cells and promoted glucose consumption in mouse 3T3-L1 cells.  These results give us valuable information as to the chemical structure-effect relationship of DIF-1. Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp] -------------------------------------------------------------------------------- A UDP-glucose derivative is required for vacuolar autophagic cell death Emilie Tresse, Artemis Kosta, Corinne Giusti, Marie-Françoise Luciani and Pierre Golstein Autophagy, 2008, 4, 680-691 Autophagic cell death in Dictyostelium can be dissociated into a starvation-induced sensitization stage and a death induction stage. A UDP-glucose pyrophosphorylase (ugpB) mutant and a glycogen synthase (glcS) mutant shared the same abnormal phenotype. In vitro, upon starvation alone mutant cells showed altered contorted morphology, indicating that the mutations affected the pre-death sensitization stage. Upon induction of cell death, most of these mutant cells underwent death without vacuolization, distinct from either autophagic or necrotic cell death. Autophagy itself was not grossly altered as shown by conventional and electron microscopy. Exogenous glycogen or maltose could complement both ugpB- and glcS- mutations, leading back to autophagic cell death. The glcS- mutation could also be complemented by 2-deoxyglucose that cannot undergo glycolysis. In agreement with the in vitro data, upon development glcS- stalk cells died but most were not vacuolated. We conclude that a UDP-glucose derivative (such as glycogen or maltose) plays an essential energy-independent role in autophagic cell death. Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr] -------------------------------------------------------------------------------- Marked mitochondrial alterations upon starvation without cell death, caspases or Bcl-2 family members Artemis Kosta, Marie-Françoise Luciani, Willie J.C. Geerts, Pierre Golstein Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1783, Issue 10, October 2008, Pages 2013-2019 Dictyostelium HMX44A cells can withstand starvation under monolayer conditions for a few days without dying. They die only when the differentiation factor DIF-1 is exogenously added. Still, when HMX44A were subjected to starvation without addition of DIF-1 they showed, by electron microscopy and electron tomography, gross mitochondrial lesions including marked cristae alterations with frequent “holes” probably originating from dilated cristae. Since these cells did not die as shown for instance by FACS analysis, these results showed unexpected resilience of cells bearing markedly altered mitochondria, and thus showed that apparently destructive mitochondrial alterations may not lead to cell death. Also, these marked mitochondrial lesions could not be caused by caspases or bcl-2 family members, which these cells do not encode. Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr] -------------------------------------------------------------------------------- Necrotic cell death : From reversible mitochondrial uncoupling to irreversible lysosomal permeabilization Corinne Giusti, Marie-Françoise Luciani, Gérard Klein, Laurence Aubry, Emilie Tresse, Artemis Kosta, Pierre Golstein Experimental Cell Research, In Press, Accepted Manuscript, Available online 11 October 2008 Dictyostelium atg1- mutant cells provide an experimentally and genetically favorable model to study necrotic cell death (NCD) with no interference from apoptosis orautophagy. In such cells subjected to starvation and cAMP, induction by the differentiation-inducing factor DIF or by classical uncouplers led within minutes to mitochondrial uncoupling, which causally initiated NCD. We now report that (1) in this model, NCD included a mitochondrial-lysosomal cascade of events, (2) mitochondrial uncoupling and therefore initial stages of death showed reversibility for a surprisingly long time, (3) subsequent lysosomal permeabilization could be demonstrated using Lysosensor blue, acridin orange, Texas red-dextran and cathepsin B substrate, (4) this lysosomal permeabilization was irreversible, and (5) the presence of the uncoupler was required to maintain mitochondrial lesions but also to induce lysosomal lesions, suggesting that signaling from mitochondria to lysosomes must be sustained by the continuous presence of the uncoupler. These results further characterized the NCD pathway in this priviledged model, contributed to a definition of NCD at the lysosomal level, and suggested that in mammalian NCD even late reversibility attempts by removal of the inducer may be of therapeutic interest. Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr] ============================================================== [End dictyNews, volume 31, number 13]