M(en)TORship lessons on life and death by the integrated stress response

Cells employ pro-survival and pro-adaptive pathways to cope with different forms of environmental stress. When stress is excessive, and the damage caused by it is unsustainable, cells engage pro-death pathways, which are in place to protect the host from the deleterious effects of harmed cells. Two important pathways that determine the balance between survival and death of stressed cells are the integrated stress response (ISR) and the mammalian target of rapamycin (mTOR), both of which converge at the level of mRNA translation. The two pathways have established avenues of communication to control their activity and determine the fate of stressed cells in a context-dependent manner. The functional interplay between the ISR and mTOR may have significant ramifications in the development and treatment of human diseases such as diabetes, neurodegeneration and cancer.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Heliothrix oregonensis,gen. nov., sp. nov., a phototrophic filamentous gliding bacterium containing bacteriochlorophyll a

An unusual filamentous, gliding bacterium was found in a few hot springs in Oregon where it formed a nearly unispecific top layer of microbial mats. It contained a bacteriochlorophyll a-like pigment and an abundance of carotenoids. There were no chlorosomes or additional chlorophylls. The organism was aerotolerant and appeared to be photoheterotrophic. It was successfully co-cultured with an aerobic chemoheterotroph in a medium containing glucose and casamino acids. Although it has many characteristics in common with the genus Chloroflexus, the lack of chlorosomes and bacteriochlorophyll c and the aerobic nature of this organism indicate that it should be placed in a new genus. This conclusion is supported by 5S rRNA nucleotide sequence data.     

Ultrastructural changes in isolated rat hepatocytes exposed to different CCl4 concentrations

Ultrastructural data are presented on time-course changes in isolated rat hepatocyte suspensions exposed either to 1.2 or 1.8 mM CCl4 for up to 1 h. The subcellular changes at the lower concentration, but not the higher, are shown to closely parallel those reported to occur in rat hepatocytes following ingestion of CCl4.     

Pre-emptive Quality Control of a Misfolded Membrane Protein by Ribosome-Driven Effects

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Effects of Organic Solvents on the Coupling Between ATP Hydrolysis and Sliding of Microtubules in Axonemes from Chlamydomonas Flagella

ABSTRACT. The effects of organic solvents on the ATPase activity and the sliding disintegration of axonemes from Chlamydomonas were investigated. The axonemal ATPase was markedly activated by methanol accompanying with marked inhibition of the sliding disintegration of axonemes. On the contrary, glycerol inhibited the ATPase activity without serious inhibition of the sliding disintegration. As far as the axonemes are not irreversibly denatured by extremely high concentration of solvents, the effects of solvents both on the ATPase and the ability of sliding are reversible. Therefore, the inhibition of sliding accompanied by the activation of ATPase is probably due to an inability to couple the hydrolysis of ATP to sliding between dynein and microtubule in the presence of methanol. The axonemal ATPase was less sensitive to vanadate inhibition after exposure to methanol. This indicates that methanol makes the dyneinADP.Pi complex unstable and increases product release. On the other hand, glycerol and ethylene glycol seem to stabilize the force generation responsible for the sliding through stabilizing the dynein.ADP.Pi complex.