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Mitochondrial outer membrane permeability

Takahiro Shibata, Mayu Yoneda, Daisuke Morikawa, Yoshihiro Ohta
Mitochondrial functions are closely related to the membrane structure. Mitochondrial swelling, which is accompanied with dissipation of the crista structure and rupture of the outer membrane, have been observed as mitochondrial damage when mitochondria are under Ca2+ -overload or oxidative stress. Although these phenomena have been well studied, the detailed behaviors of individual mitochondria upon swelling remain unknown. The aim of this study was to investigate the detailed behavior of mitochondrial volume upon addition of Ca2+ ...
January 16, 2019: Archives of Biochemistry and Biophysics
Sofhia V Ramos, Meghan C Hughes, Christopher G R Perry
Microtubule-targeting chemotherapies are linked to impaired cellular metabolism which may contribute to skeletal muscle dysfunction. However, the mechanisms by which metabolic homeostasis is perturbed remains unknown. Tubulin, the fundamental unit of microtubules, has been implicated in the regulation of mitochondrial-cytosolic ADP/ATP exchange through its interaction with the outer membrane voltage-dependent anion channel (VDAC). Based on this model, we predicted that disrupting microtubule architecture with the stabilizer paclitaxel and destabilizer vinblastine would impair skeletal muscle mitochondrial bioenergetics...
January 9, 2019: American Journal of Physiology. Cell Physiology
Hector Flores-Romero, Olatz Landeta, Begoña Ugarte-Uribe, Katia Cosentino, Miguel García-Porras, Ana J García-Sáez, Gorka Basañez
BFL1 is a relatively understudied member of the BCL2 protein family which has been implicated in the pathogenesis and chemoresistance of a variety of human cancers, including hematological malignancies and solid tumours. BFL1 is generally considered to have an antiapoptotic function, although its precise mode of action remains unclear. By quantitatively analyzing BFL1 action in synthetic membrane models and in cells, we found that BFL1 inhibits apoptosis through three distinct mechanisms which are similar but not identical to those of BCLXL, the paradigmatic antiapoptotic BCL2 family protein...
December 18, 2018: Cell Death and Differentiation
Salik Hussain
Mitochondria hold a critical role in cell metabolism and homeostasis. Mitochondrial injury plays central part in deciding cell fate especially in programmed cell death pathways. Various nanomaterials lead to different cell death modalities by inducing mitochondrial injury. Mitochondrial injury is manifested as multiple biochemical events ranging from altered energy production, mitochondrial outer membrane permeability, release of pro-apoptotic BCl-2 family proteins, loss of mitochondrial inner membrane potential, mitochondrial swelling, and disruption of mitochondrial structure leading to eventual lysis of mitochondria...
2019: Methods in Molecular Biology
Jialing Lin, Arthur E Johnson, Zhi Zhang
The Bcl-2 family of proteins regulates mitochondrial outer membrane permeability thereby making life or death decisions for cells. Most of Bcl-2 proteins contain hydrophobic regions that are embedded in intracellular membranes such as mitochondria. These membrane proteins are difficult to express and purify thereby preluding biochemical and biophysical characterizations. Here, we describe a photocrosslinking approach based on in vitro synthesis of Bcl-2 proteins with photoreactive amino acid analogs incorporated at specific locations...
2019: Methods in Molecular Biology
A Y Mulkidjanian, D N Shalaeva, K G Lyamzaev, B V Chernyak
Oxidative stress causes selective oxidation of cardiolipin (CL), a four-tail lipid specific for the inner mitochondrial membrane. Interaction with oxidized CL transforms cytochrome c into peroxidase capable of oxidizing even more CL molecules. Ultimately, this chain of events leads to the pore formation in the outer mitochondrial membrane and release of mitochondrial proteins, including cytochrome c, into the cytoplasm. In the cytoplasm, cytochrome c promotes apoptosome assembly that triggers apoptosis (programmed cell death)...
October 2018: Biochemistry. Biokhimii︠a︡
Siqi Zhou, Haiyan Wen, Weisong Cai, Yubiao Zhang, Haohuan Li
Hypoxia/reoxygenation (H/R) plays an important role in the pathogenesis of osteoarthritis. Fibroblast-like synoviocytes (FLS), which are highly sensitive to H/R, are thought to be associated with cartilage degradation during osteoarthritis development. In this study, we investigated the biological effects of insulin-like growth factor (IGF) system and the expression of inflammatory mediators in FLS. We also pretreated FLS with tumor necrosis factor-α (TNF-α) before H/R in order to observe the response of FLS with the background of inflammatory cytokines...
November 19, 2018: Biochemical and Biophysical Research Communications
Luigi Leanza, Vanessa Checchetto, Lucia Biasutto, Andrea Rossa, Roberto Costa, Magdalena Bachmann, Mario Zoratti, Ildiko Szabo
The field of mitochondrial ion channels has undergone a rapid development during the last three decades, due to the molecular identification of some of the channels residing in the outer and inner membranes. Relevant information about the function of these channels in physiological and pathological settings was gained thanks to genetic models for a few, mitochondria-specific channels. However, many ion channels have multiple localization within the cell hampering a clear-cut determination of their function by pharmacological means...
November 15, 2018: British Journal of Pharmacology
Adel Rezaei Moghadam, Simone C da Silva Rosa, Ehsan Samiei, Javad Alizadeh, Jared Field, Philip Kawalec, James Thliveris, Mohsen Akbari, Saeid Ghavami, Joseph W Gordon
Rhabdomyosarcoma (RMS) is a muscle-derived tumor. In both pre-clinical and clinical studies Temozolomide (TMZ) has been recently tested against RMS; however, the precise mechanism of action of TMZ in RMS remains unclear. Here we demonstrate that TMZ decreases the cell viability of the RH30 RMS and C2C12 cell line, where cells display evidence of mitochondrial outer membrane permeability. Interestingly, the C2C12 mouse myoblast line was relatively more resistant to TMZ-induced apoptosis. Moreover, we observed that TMZ activated biochemical and morphological markers of autophagy in both cell lines...
2018: Cell Death Discovery
María Queralt-Martín, Lucie Bergdoll, Daniel Jacobs, Sergey M Bezrukov, Jeff Abramson, Tatiana K Rostovtseva
The voltage-dependent anion channel (VDAC) is the most abundant protein of the mitochondrial outer membrane (MOM) where it regulates transport of ions and metabolites in and out of the organelle. VDAC function is extensively studied in a lipid bilayer system that allows conductance monitoring of reconstituted channels under applied voltage. The process of switching from a high-conductance state, open to metabolites, to a variety of low-conducting states, which excludes metabolite transport, is termed voltage gating and the mechanism remains poorly understood...
November 6, 2018: Biochimica et biophysica acta. Bioenergetics
Shamim Naghdi, William S Slovinsky, Muniswamy Madesh, Emanuel Rubin, György Hajnóczky
Environmental stressors like ethanol (EtOH) commonly target mitochondria to influence the cell's fate. Recent literature supports that chronic EtOH exposure suppresses mitochondrial dynamics, central to quality control, and sensitizes mitochondrial permeability transition pore opening to promote cell death. EtOH-induced tissue injury is primarily attributed to its toxic metabolic products but alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on studies to determine the respective roles of EtOH and its metabolites in mitochondrial fusion and tBid-induced mitochondrial apoptosis...
October 9, 2018: Cell Death & Disease
Victor V Lemeshko
Glycolysis plays a key role in brain energy metabolism. The initial and rate-limiting step of brain glycolysis is catalyzed mainly by hexokinase I (HKI), the majority of which is bound to the mitochondrial outer membrane (MOM), mostly through the mitochondrial inter-membrane contact sites formed by the voltage-dependent anion channel (VDAC, outer membrane) and the adenine nucleotide translocator (ANT, inner membrane). Earlier, we proposed a mechanism for the generation of the mitochondrial outer membrane potential (OMP) as a result of partial application of the inner membrane potential (IMP) to MOM through the electrogenic ANT-VDAC-HK inter-membrane contact sites...
December 2018: Biochimica et biophysica acta. Biomembranes
Vincenzo Zara, Alessandra Ferramosca, Kathrin Günnewig, Sebastian Kreimendahl, Jan Schwichtenberg, Dina Sträter, Mahmut Çakar, Kerstin Emmrich, Patrick Guidato, Ferdinando Palmieri, Joachim Rassow
Mimivirus (Acanthamoeba polyphaga mimivirus) was the first giant DNA virus identified in an amoeba species. Its genome contains at least 979 genes. One of these, L276, encodes a nucleotide translocator with similarities to mitochondrial metabolite carriers, provisionally named viral mitochondrial carrier 1 (VMC1). In this study, we investigated the intracellular distribution of VMC1 upon expression in HeLa cells and in the yeast Saccharomyces cerevisiae. We found that VMC1 is specifically targeted to mitochondria and to the inner mitochondrial membrane...
September 25, 2018: Journal of Molecular Biology
Zeyu Zhang, Huan He, Yang Qiao, Jiyi Huang, Zelong Wu, Ping Xu, Dong Yin, Ming He
Tanshinone IIA is an important component that is isolated from danshen ( Salvia miltiorrhiza ), which is known to be beneficial for cardiovascular health. In this study, we determined the effects of Tanshinone IIA and its underlying mechanisms of action in an anoxia/reoxygenation (A/R) cell line model. Prior to inducing A/R injury, rat cardiomyocyte-derived cell line H9c2 was stimulated with 8  μ M of Tanshinone IIA for 48 hours. When compared with the A/R group, the Tanshinone IIA treatment significantly increased cell viability and decreased lactate dehydrogenase activity...
2018: Oxidative Medicine and Cellular Longevity
Aleksandr Klepinin, Lyudmila Ounpuu, Kati Mado, Laura Truu, Vladimir Chekulayev, Marju Puurand, Igor Shevchuk, Kersti Tepp, Anu Planken, Tuuli Kaambre
Previous studies have shown that class II β-tubulin plays a key role in the regulation of oxidative phosphorylation (OXPHOS) in some highly differentiated cells, but its role in malignant cells has remained unclear. To clarify these aspects, we compared the bioenergetic properties of HL-1 murine sarcoma cells, murine neuroblastoma cells (uN2a) and retinoic acid - differentiated N2a cells (dN2a). We examined the expression and possible co-localization of mitochondrial voltage dependent anion channel (VDAC) with hexokinase-2 (HK-2) and βII-tubulin, the role of depolymerized βII-tubuline and the effect of both proteins in the regulation of mitochondrial outer membrane (MOM) permeability...
July 12, 2018: Journal of Bioenergetics and Biomembranes
Sonata Trumbeckaite, Vaidotas Cesna, Aldona Jasukaitiene, Rasa Baniene, Antanas Gulbinas
Gastrointestinal cancers (gastric, pancreatic and colorectal) are life-threatening diseases, which easily spread to peritoneal cavity (Juhl et al. in Int J Cancer 57:330-335, 1994; Schneider et al. in Gastroenterology 128:1606-1625, 2005; Geer and Brennan in Am J Surg 165:68-72 1993). Application of hyperthermal intraperitoneal chemotherapy (HIPEC) is one of the choices treating these malignancies and prolonging patient survival time. Despite numbers of clinical trials showing positive effects of HIPEC against various types of cancer, the question whether hyperthermia significantly potentiate the cytotoxicity of cisplatin remains unanswered...
October 2018: Journal of Bioenergetics and Biomembranes
Yoo Jin Lee, Changhee Lee
Porcine deltacoronavirus (PDCoV), a newly discovered enteric coronavirus, is a causative agent of severe clinical diarrhea and intestinal pathological damage in piglets. As a first step toward understanding the effect of PDCoV on host cells, we elucidated mechanisms underlying the process of apoptotic cell death after PDCoV infection. The use of a pan-caspase inhibitor resulted in the inhibition of PDCoV-induced apoptosis and reduction of PDCoV replication, suggestive of the association of a caspase-dependent pathway...
July 15, 2018: Virus Research
Ljudmila S Khailova, Tatyana I Rokitskaya, Sergey I Kovalchuk, Еlena А Kotova, Alexandra I Sorochkina, Yuri N Antonenko
Of a series of gramicidin A (gA) derivatives, we have earlier found the peptide [Glu1]gA exhibiting very low toxicity toward mammalian cells, although dissipating mitochondrial membrane potential with almost the same efficiency as gA. Substitution of glutamate for valine at position 1 of the gA amino acid sequence, which is supposed to interfere with the formation of ion-conducting gA channels via head-to-head dimerization, reduces both channel-forming potency of the peptide in planar lipid bilayer membranes and its photonophoric activity in unilamellar liposomes...
June 22, 2018: Biochimica et biophysica acta. Biomembranes
Farhan Younas, Nafiseh Soltanmohammadi, Oliver Knapp, Roland Benz
Legionella pneumophila is an aerobic and nonspore-forming pathogenic Gram-negative bacterium of the genus Legionella. It is the causative agent of Legionnaires' disease, also known as Legionellosis. The hosts of this organism are diverse, ranging from simple water borne protozoans such as amoebae to more complex hosts such as macrophages in humans. Genome analyses have shown the presence of genes coding for eukaryotic like proteins in several Legionella species. The presence of these proteins may assist L. pneumophila in its adaptation to the eukaryotic host...
August 2018: Biochimica et biophysica acta. Biomembranes
Tatiana K Rostovtseva, Philip A Gurnev, David P Hoogerheide, Amandine Rovini, Minhajuddin Sirajuddin, Sergey M Bezrukov
The microtubule protein tubulin is a heterodimer comprising α/β subunits, in which each subunit features multiple isotypes in vertebrates. For example, seven α-tubulin and eight β-tubulin isotypes in the human tubulin gene family vary mostly in the length and primary sequence of the disordered anionic carboxyl-terminal tails (CTTs). The biological reason for such sequence diversity remains a topic of vigorous enquiry. Here, we demonstrate that it may be a key feature of tubulin's role in regulation of the permeability of the mitochondrial outer membrane voltage-dependent anion channel (VDAC)...
July 13, 2018: Journal of Biological Chemistry
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