Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein

Although endolysosomal trafficking is well defined, how it is regulated and coordinates with cellular metabolism is unclear. To identify genes governing endolysosomal dynamics, we conducted a global fluorescence-based screen to reveal endomembrane effector genes. Screening implicated Phox (PX) domain-containing protein Mdm1 in endomembrane dynamics. Surprisingly, we demonstrate that Mdm1 is a novel interorganelle tethering protein that localizes to endoplasmic reticulum (ER)-vacuole/lysosome membrane contact sites (MCSs). We show that Mdm1 is ER anchored and contacts the vacuole surface in trans via its lipid-binding PX domain. Strikingly, overexpression of Mdm1 induced ER-vacuole hypertethering, underscoring its role as an interorganelle tether. We also show that Mdm1 and its paralogue Ydr179w-a (named Nvj3 in this study) localize to ER-vacuole MCSs independently of established tether Nvj1. Finally, we find that Mdm1 truncations analogous to neurological disease-associated SNX14 alleles fail to tether the ER and vacuole and perturb sphingolipid metabolism. Our work suggests that human Mdm1 homologues may play previously unappreciated roles in interorganelle communication and lipid metabolism

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Main drivers for settlement of creative and knowledge intensive companies in the Budapest Metropolitan Region. The managers' view

© 2017 European Association of Geochemistry. Multiple stable isotope relationships have found a growing variety of uses in geochemistry and cosmochemistry. Approximations to the statistical-mechanical models for predicting isotope effects have led to the notion that mass fractionation laws are constrained to a canonical range of possible values. Despite previous work indicating that these mass fractionation exponents can be highly variable, the concept of a constant relationship remains common. In this study, we demonstrate generically that the mass fractionation exponent, θ, can take any value for small fractionations and that these deviations are measurable. In addition, we characterise and advocate the use of the change/difference in cap-delta as a necessary and more reliable descriptor of multiple isotope fractionation relationships. Deviations from the canonical range are demonstrated by experimental data in the geochemically relevant haematite-water system

Heat shock lipid” in cyanobacteria during heat/light-acclimation.

Parallel with the heat/light-induced thylakoid microdomain reorganization and thermal stabilization of photosynthesis we observed an increase in the level of the highly saturated monoglucosyldiacylglycerol (MGlcDG) in Synechocystis cells. The unusually high microviscosity obtained in thylakoid MGlcDG liposomes by monitoring DPH anisotropy was in good agreement with its exceptionally high acyl chain saturation. The MGlcDG membranes remained stable even at extreme high temperatures. Strikingly, in monolayer experiments, out of the five thylakoid polar lipids tested, MGlcDG expressed the strongest interaction with the thylakoid-stabilizing small Hsp from Synechocystis, Hsp17. The preferential interaction of Hsp17 with non-bilayer phase forming lipids supports our notion that sHsps counteract the formation of thermally induced local non-bilayer structures [Proc. Natl. Acad. Sci. USA 99 (2002) 13504] and thus implicated in microdomain organization and in the preservation of functional integrity of thylakoid membranes challenged by heat stress in the light. We also suggest that the highly saturated MGlcDG functions as a “heat shock lipid” and is of potential importance in the development of acquired thermotolerance of heat/light-primed cyanobacterial thylakoids