The Cytosolic Domain of Fis1 Binds and Reversibly Clusters Lipid Vesicles

Every lipid membrane fission event involves the association of two apposing bilayers, mediated by proteins that can promote membrane curvature, fusion and fission. We tested the hypothesis that Fis1, a tail-anchored protein involved in mitochondrial and peroxisomal fission, promotes changes in membrane structure. We found that the cytosolic domain of Fis1 alone binds lipid vesicles, which is enhanced upon protonation and increasing concentrations of anionic phospholipids. Fluorescence and circular dichroism data indicate that the cytosolic domain undergoes a membrane-induced conformational change that buries two tryptophan side chains upon membrane binding. Light scattering and electron microscopy data show that membrane binding promotes lipid vesicle clustering. Remarkably, this vesicle clustering is reversible and vesicles largely retain their original shape and size. This raises the possibility that the Fis1 cytosolic domain might act in membrane fission by promoting a reversible membrane association, a necessary step in membrane fission

Mitochondrial Fragmentation Is Involved in Methamphetamine-Induced Cell Death in Rat Hippocampal Neural Progenitor Cells

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen species (ROS), but not calcium (Ca2+) influx, were involved in the regulation of METH-induced mitochondrial fragmentation. Furthermore, our results indicated that dysregulation of ROS contributed to the oligomerization and translocation of Drp1, resulting in mitochondrial fragmentation in rhNPC. Taken together, our data demonstrate that METH-mediated ROS generation results in the dysregulation of Drp1, which leads to mitochondrial fragmentation and subsequent apoptosis in rhNPC. This provides a potential mechanism for METH-related neurodegenerative disorders, and also provides insight into therapeutic strategies for the neurodegenerative effects of METH

Dynamics of water in partially crystallized solutions of glass forming materials and polymers: Implications on the behavior of bulk water

There is no simpler compound than water. It is the most copious substance on Earth and the most important constituent for life, as we know. There is also a continuous scientific interest due to its exceptional and infrequent properties, such as a density maximum at 4 ℃ (at atmospheric pressure), a high specific heat capacity, and a low viscosity under high pressure, among other macroscopic properties. The origin of the unusual properties of water is evidenced at lower temperatures in the no man’s land temperature region (235–150 K), where bulk water cannot remain in an amorphous state. Instead, in this region, bulk water crystallizes in a complex phase diagram with more than 16 crystalline phases. Therefore, most of the work done so far on supercooled water focuses on the investigation of the dynamics when crystallization is suppressed using different types of confinements, such as nano-cavities or by mixing water with other solutes (polymers, proteins, or DNA). On the contrary, in this chapter, we will use broadband dielectric spectroscopy to analyze the dynamics of aqueous solutions and confined water when it is partially crystallized, i.e., when liquid water and ice coexist. With this technique, it is possible to obtain information about the molecular relaxations in both amorphous and crystalline phases. We have analyzed the results of this semi-crystalline water and compared them with the response of supercooled water in fully amorphous solutions. Finally, we discuss the implications of these results on the behavior of bulk water.The authors gratefully acknowledge CSIC (i-LINK + program LINKB 20012), Spanish Ministerio de Ciencia, Innovacion y Universidades code: PID2019-104650GB-C21 (MCIU/AEI/FEDER, UE) and the Swedish Research Council (grant no. 2015-05434).Peer reviewe