56 research outputs found
The signal sequence receptor, unlike the signal recognition particle receptor, is not essential for protein translocation
Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins
Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic relocalization of eEF1A by the HIV-1 Nef protein
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t, occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin-A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages
The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex
BAAV Transcytosis Requires an Interaction with β-1-4 Linked- Glucosamine and gp96
Cell surface carbohydrates play an important role in virus entry and intracellular trafficking. Bovine Adeno-Associated Virus (BAAV) uses plasma membrane gangliosides for transduction and infection. In addition, independent of the infectious pathway, BAAV also has the ability to pass through barrier epithelia and endothelia using a transcytosis pathway dependent upon the presence of cell surface carbohydrates. Thus, in order to better define the carbohydrate interactions that are necessary for BAAV infection or transcytosis, a glycan microarray composed of both natural and synthetic carbohydrates was probed with HA-tagged BAAV particles. This identified chitotriose, a trimer of β-1-4-linked N-acetyl glucosamine, as having an interaction with BAAV. Competition experiments showed that the BAAV interaction with this carbohydrate is not necessary for infection but is instead important in the transcytosis pathway. The β-1-4-linked N-acetyl glucosamine modification has been reported on gp96, a glycoprotein involved in the transcytosis of bacteria and toxins. Significantly, immunoprecipitation and competition experiments with an anti-gp96 antibody and a soluble form of gp96, respectively, showed this glycoprotein can also interact with BAAV to serve as a receptor for its transcytosis
Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis
Inflammation is a necessary albeit insufficient component of tumorigenesis in some cancers. Infectious agents directly implicated in tumorigenesis have been shown to induce inflammation. This process involves both the innate and adaptive components of the immune system which contribute to tumor angiogenesis, tumor tolerance and metastatic properties of neoplasms. Recently, heat-shock proteins have been identified as mediators of this inflammatory process and thus may provide a link between infection-mediated inflammation and subsequent cancer development. In this review, the role of heat-shock proteins in infection-induced inflammation and carcinogenesis will be discussed
Bidirectional fluxes of spermine across the mitochondrial membrane.
The polyamine spermine is transported into the
mitochondrial matrix by an electrophoretic mechanism
having as driving force the negative electrical membrane
potential (DW). The presence of phosphate increases
spermine uptake by reducingDpH and enhancingDW. The
transport system is a specific uniporter constituted by a
protein channel exhibiting two asymmetric energy barriers
with the spermine binding site located in the energy well
between the two barriers. Although spermine transport is
electrophoretic in origin, its accumulation does not follow
the Nernst equation for the presence of an efflux pathway.
Spermine efflux may be induced by different agents, such as
FCCP, antimycin A and mersalyl, able to completely or
partially reduce theDWvalue and, consequently, suppress
or weaken the force necessary to maintain spermine in the
matrix. However this efflux may also take place in normal
conditions when the electrophoretic accumulation of the
polycationic polyamine induces a sufficient drop inDWable
to trigger the efflux pathway. The release of the polyamine
is most probably electroneutral in origin and can take place
in exchange with protons or in symport with phosphate
anion. The activity of both the uptake and efflux pathways
induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and
outer compartment. Thus, this event has a significant role on
mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis
Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins
Direct augmentation by cyclosporin A of the vascular contractile response to nerve stimulation.
Mitochondrial calcium uniporter complex activation protects against calcium alternans in atrial myocytes
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