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Mitochondrial outer membrane permeability

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...
October 4, 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...
June 25, 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
Lara Macchioni, Maya Petricciuolo, Magdalena Davidescu, Katia Fettucciari, Paolo Scarpelli, Rita Vitale, Leonardo Gatticchi, Pier Luigi Orvietani, Andrea Marchegiani, Pierfrancesco Marconi, Gabrio Bassotti, Angela Corcelli, Lanfranco Corazzi
Enteric glial cells (EGCs) are components of the enteric nervous system, an organized structure that controls gut functions. EGCs may be vulnerable to different agents, such as bacterial infections that could alter the intestinal epithelial barrier, allowing bacterial toxins and/or other agents possessing intrinsic toxic effect to access cells. Palmitate, known to exhibit lipotoxicity, is released in the gut during the digestion process. In this study, we investigated the lipotoxic effect of palmitate in cultured EGCs, with particular emphasis on palmitate-dependent intracellular lipid remodeling...
August 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Seiji Kojima, Masayuki Iwamoto, Shigetoshi Oiki, Saeko Tochigi, Hideyuki Takahashi
The thylakoid lumen is a membrane-enclosed aqueous compartment. Growing evidence indicates that the thylakoid lumen is not only a sink for protons and inorganic ions translocated during photosynthetic reactions but also a place for metabolic activities, e.g. proteolysis of photodamaged proteins, to sustain efficient photosynthesis. However, the mechanism whereby organic molecules move across the thylakoid membranes to sustain these lumenal activities is not well understood. In a recent study of Cyanophora paradoxa chloroplasts (muroplasts), we fortuitously detected a conspicuous diffusion channel activity in the thylakoid membranes...
May 18, 2018: Journal of Biological Chemistry
Kilmer S McCully
The indoleamine hormone melatonin is synthesized by the pineal gland, controls circadian rhythm, and is dependent upon adenosyl methionine for enzymatic synthesis of melatonin from N-acetyl serotonin. Pineal melatonin secretion declines dramatically with aging and dementia. Elevated plasma homocysteine is a risk factor for atherosclerosis and Alzheimer's disease, and the marked decline in adenosyl methionine with aging leads to dysregulation of methionine metabolism and hyperhomocysteinemia. Thioretinaco ozonide is a disulfonium complex formed from thioretinamide, cobalamin, and ozone, which binds the alpha and gamma-phosphate groups of adenosine triphosphate (ATP) and oxygen in the process of oxidative phosphorylation within mitochondria...
January 2018: Annals of Clinical and Laboratory Science
Bong Sook Jhun, Jin O-Uchi, Stephanie M Adaniya, Thomas J Mancini, Jessica L Cao, Michelle E King, Amy K Landi, Hanley Ma, Milla Shin, Donqin Yang, Xiaole Xu, Yisang Yoon, Gaurav Choudhary, Richard T Clements, Ulrike Mende, Shey-Shing Sheu
KEY POINTS: Abnormal mitochondrial morphology and function in cardiomyocytes are frequently observed under persistent Gq protein-coupled receptor (Gq PCR) stimulation. Cardiac signalling mechanisms for regulating mitochondrial morphology and function under pathophysiological conditions in the heart are still poorly understood. We demonstrate that a downstream kinase of Gq PCR, protein kinase D (PKD) induces mitochondrial fragmentation via phosphorylation of dynamin-like protein 1 (DLP1), a mitochondrial fission protein...
March 1, 2018: Journal of Physiology
H-R Lee, Y Y Cho, G Y Lee, D-G You, Y D Yoo, Y J Kim
Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process...
April 2018: Journal of Viral Hepatitis
Katarzyna Niedzwiecka, Renata Tisi, Sara Penna, Malgorzata Lichocka, Danuta Plochocka, Roza Kucharczyk
The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6-P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP...
January 2018: Biochimica et biophysica acta. Molecular cell research
Zhiyong Yin, Hong Qi, Lili Liu, Zhen Jin
In most cell types, apoptosis occurs by the mitochondrial outer membrane permeability (MOMP)-mediated pathway, which is controlled by Bcl-2 family proteins (often referred to as Bcl-2 apoptotic switch). These proteins, which display a range of bioactivities, can be divided into four types: effectors, inhibitors, activators and sensitizers. Although the complex interactions among Bcl-2 family members have been studied intensively, a unifying hypothesis for the mechanism they use to regulate MOMP remains elusive...
December 2017: Bio Systems
Evangelos Giampazolias, Barbara Zunino, Sandeep Dhayade, Florian Bock, Catherine Cloix, Kai Cao, Alba Roca, Jonathan Lopez, Gabriel Ichim, Emma Proïcs, Camila Rubio-Patiño, Loic Fort, Nader Yatim, Emma Woodham, Susana Orozco, Lucia Taraborrelli, Nieves Peltzer, Daniele Lecis, Laura Machesky, Henning Walczak, Matthew L Albert, Simon Milling, Andrew Oberst, Jean-Ehrland Ricci, Kevin M Ryan, Karen Blyth, Stephen W G Tait
Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis...
September 2017: Nature Cell Biology
Ibai Artetxe, Begoña Ugarte-Uribe, David Gil, Mikel Valle, Alicia Alonso, Ana J García-Sáez, Félix M Goñi
Ceramide is a sphingolipid involved in several cellular processes, including apoptosis. It has been proposed that ceramide forms large and stable channels in the mitochondrial outer membrane that induce cell death through direct release of cytochrome c. However, this mechanism is still debated because the membrane permeabilizing activity of ceramide remains poorly understood. To determine whether the mechanism of ceramide-induced membrane leakage is consistent with the hypothesis of an apoptotic ceramide channel, we have used here assays of calcein release from liposomes...
August 22, 2017: Biophysical Journal
Zhihong Tong, Yongyan Xie, Ming He, Wen Ma, Yue Zhou, Songqing Lai, Yan Meng, Zhangping Liao
We have recently demonstrated that Voltage-dependent anion channel 1 (VDAC1), a protein located in the mitochondrial outer membrane, is involved in the effects of resveratrol on the mitochondrial permeability transition pore (mPTP). However, the underlying mechanism of action remains to be elucidated. In the present study, we demonstrated that resveratrol promoted VDAC1 deacetylation in cardiomyocytes in response to anoxia/reoxygenation (A/R) injury. Moreover, silent information regulator of transcription 1 (SIRT1), a NAD+ -dependent class III histone deacetylase, was up-regulated after pretreatment with resveratrol...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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