Please use this identifier to cite or link to this item:
https://repositorio.accefyn.org.co/handle/001/1011
Cómo citar
Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Lemeshko, Viktor V. | - |
| dc.date.accessioned | 2021-11-15T15:22:04Z | - |
| dc.date.available | 2021-11-15T15:22:04Z | - |
| dc.date.issued | 2018-04-13 | - |
| dc.identifier.uri | https://repositorio.accefyn.org.co/handle/001/1011 | - |
| dc.description.abstract | Hasta 95 % de la energía en las células eucariotas se produce en las mitocondrias, las cuales se componen de dos membranas, la interna y la externa. La principal función de la membrana interna es la fosforilación oxidativa. El trifosfato de adenosina (adenosine triphosphate, ATP) y el fosfato de creatina, producidos en las mitocondrias, se transfieren al citosol atravesando la membrana mitocondrial externa, básicamente a través de las porinas (voltagedependent anion cannel, VDAC). Dado que los mecanismos de generación del potencial eléctrico en esta membrana se desconocen, generalmente se asume que la compuerta eléctrica de los VDAC siempre está abierta. Sin embargo, el potencial de la membrana mitocondrial externa puede generarse de manera dependiente del metabolismo energético celular mediante diversos mecanismos. La generación de dicho potencial mediante los complejos VDAC-hexocinasa en las células cancerígenas, o la oxidación directa del NADH citosólico en las mitocondrias de la levadura Saccharomyces cerevisiae permiten explicar los efectos de Crabtree y Warburg como una supresión eléctrica de las mitocondrias. Según el modelo desarrollado, la prevención de la formación de los complejos VDAC-hexocinasa por acción de algunos factores podría causar efectos anti-Warburg y anticancerígenos. Además, este potencial positivo generado por los complejos VDAC-creatina-cinasa podría proteger las mitocondrias de los cardiomiocitos y de otras células frente a los niveles tóxicos de calcio en el citosol. Los mecanismos propuestos de generación del potencial de la membrana dependiente del metabolismo energético celular, sugieren que las propiedades eléctricas del VDAC tienen un papel importante en varios procesos fisiológicos y patofisiológicos. | spa |
| dc.description.abstract | Up to 95% of the energy in the eukaryotic cells is produced in the mitochondria, which are composed of two membranes, internal and external. The main function of the inner membrane is the oxidative phosphorylation. ATP and/or phosphocreatine produced in mitochondria are transferred to the cytosol across the mitochondrial outer membrane, mainly through the porins (voltage-dependent anion channel, VDAC). As the mechanisms of generation of the electrical potential on this membrane are not known, it is generally assumed that the VDAC electric gate is always open. However, the outer membrane potential (OMP) of mitochondria may be generated by various mechanisms in a manner dependent on the cell energy metabolism. OMP generation by the VDAChexokinase complexes in cancer cells, or by the direct oxidation of cytosolic NADH in the mitochondria of the yeast Saccharomyces cerevisiae, may explain the Crabtree and Warburg effects as an electrical suppression of mitochondria. According to the model developed, the prevention of the formation of the VDAC-hexokinase complexes may result in anti- Warburg and anti-cancer effects. In addition, the generation of the positive OMP by the VDAC-creatine kinase complexes could protect mitochondria in cardiomyocytes and other cells against toxic levels of cytosolic calcium. The mechanisms proposed for OMP generation dependent on the cell energymetabolism suggest that the VDAC electrical properties play an important role in various physiological and pathophysiological processes. | eng |
| dc.format.mimetype | application/pdf | spa |
| dc.language.iso | spa | spa |
| dc.publisher | Academia Colombiana de Ciencias Exactas, Físicas y Naturales | spa |
| dc.rights | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International | spa |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | spa |
| dc.source | Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales | spa |
| dc.title | El papel de la membrana mitocondrial externa en el control del metabolismo energético celular | spa |
| dc.type | Artículo de revista | spa |
| dcterms.audience | Estudiantes, Profesores, Comunidad científica colombiana | spa |
| dcterms.references | Appaix F., Kuznetsov A.V., Usson Y., Kay L., Andrienko T., Olivares J., Kaambre T., Sikk P., Margreiter R., Saks V. (2003). Possible role of cytoskeleton in intracellular arrangement and regulation of mitochondria. Exp Physiol. 88: 175-190. | spa |
| dcterms.references | Avéret N., Aguilaniu H., Bunoust O., Gustafsson L., Rigoulet M. (2002). NADH is specifically channeled through the mitochondrial porin channel in Saccharomyces cerevisiae. J Bioenerg Biomembr. 34 (6): 499-506 | spa |
| dcterms.references | Bakker B.M., Overkamp K.M., van Maris A.J., Kötter P., Luttik M.A., van Dijken J.P., Pronk J.T. (2001). Stoichi-ometry and compartimentation of NADH metabolism in Saccharomyces cerevisiae. FEMS Microbiol Rev. 25 (1): 15-37 | spa |
| dcterms.references | Benz R., Kottke M., Brdiczka D. (1990). The cationically selective state of the mitochondrial outer membrane pore: A study with intact mitochondria and reconstituted mitochondrial porin. Biochim Biophys Acta. 1022: 311-318 | spa |
| dcterms.references | Brdiczka D.G., Zorov D.B., Sheu S.S. (2006). Mitochondrial contact sites: Their role in energy metabolism and apoptosis. Biochim. Biophys. Acta. 1762: 148-163 | spa |
| dcterms.references | Camara A.K.S., Zhou Y., Wen P.C., Tajkhorshid E., Kwok W.M. (2017). Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target. Front Physiol. 8: 460 | spa |
| dcterms.references | Carafoli E. (2012). The interplay of mitochondria with calcium: An historical appraisal. Cell Calcium. 52 (1): 1-8 | spa |
| dcterms.references | Colombini M. (1979). A candidate for the permeability pathway of the outer mitochondrial membrane. Nature. 279: 643-645. | spa |
| dcterms.references | Colombini M. (2016). The VDAC channel: Molecular basis for selectivity. Biochim Biophys Acta. 1863 (10): 2498-2502 | spa |
| dcterms.references | Colombini M., Blachly-Dyson E., Forte M. (1996). VDAC, a channel in the outer mitochondrial membrane. Ion Channels. 4: 169-202 | spa |
| dcterms.references | Colombini M., Mannella C.A. (2012). VDAC, the early days. Biochim Biophys Acta. 1818 (6): 1438-1443. | spa |
| dcterms.references | Díaz-Ruiz R., Rigoulet M., Devin A. (2011). The Warburg and Crabtree effects: On the origin of cancer cell energy metabo-lism and of yeast glucose repression. Biochim Biophys Acta. 1807 (6): 568-576 | spa |
| dcterms.references | Dolder M., Walzel B., Speer O., Schlattner U., Wallimann T. (2003). Inhibition of the mitochondrial permeability transition by creatine kinase substrates. Requirement for microcompartimentation. J Biol Chem. 278: 17760-17766 | spa |
| dcterms.references | Earnshaw M.J. (1975). The mechanism of K+-stimulated exogenous NADH oxidation in plant mitochondria. FEBS Lett. 59 (1): 109-112 | spa |
| dcterms.references | Eisner D.A., Caldwell J.L., Kistamás K., Trafford A.W. (2017). Calcium and excitation-contraction coupling in the heart. Circ Res. 121 (2): 181-195 | spa |
| dcterms.references | Hagman A., Säll T., Piškur J. (2014). Analysis of the yeast short-term Crabtree effect and its origin. FEBS J. 281 (21): 4805-4814 | spa |
| dcterms.references | Hammad N., Rosas-Lemus M., Uribe-Carvajal S., Rigoulet M., Devin A. (2016). The Crabtree and Warburg effects: Do metabolite-induced regulations participate in their induction? Biochim Biophys Acta. 1857 (8): 1139-1146 | spa |
| dcterms.references | Haridas V., Li X., Mizumachi T., Higuchi M., Lemeshko V.V., Colombini M., Gutterman J.U. (2007). Avicins, a novel plant-derived metabolite lowers energy metabolism in tumor cells by targeting the outer mitochondrial membrane. Mitochondrion. 7 (3): 234-240 | spa |
| dcterms.references | Hodge T., Colombini M. (1997). Regulation of metabolite flux through voltage-gating of VDAC channels. J Membr Biol.157 (3): 271-279 | spa |
| dcterms.references | Gerencser A.A., Chinopoulos C., Birket M.J., Jastroch M., Vitelli C., Nicholls D.G., Brand M.D. (2012). Quantitative measurement of mitochondrial membrane potential in cultured cells: Calcium-induced de- and hyperpolarization of neuronal mitochondria. J Physiol. 590 (12): 2845-2871 | spa |
| dcterms.references | John S., Weiss J.N., Ribalet B. (2011). Subcellular localization of hexokinases I and II directs the metabolic fate of glucose. PLoS One. 6 (3): e17674 | spa |
| dcterms.references | Kmita H., Budzińska M., Stobienia O. (2003). Modulation of the voltage-dependent anionselective channel by cytoplasmic proteins from wild type and the channel depleted cells of Saccharomyces cerevisiae. Acta Biochim Pol. 50 (2): 415-424. | spa |
| dcterms.references | Lemasters J.J. & Holmuhamedov E. (2006). Voltage-dependent anion channel (VDAC) as mitochondrial governator thinking outside the box. Biochim Biophys Acta. 1762 (2): 181-190. | spa |
| dcterms.references | Lemasters J.J. & Ramshesh V.K. (2007). Imaging of mito-chondrial polarization and depolarization with cationic fluorophores. Methods Cell Biol. 80: 283-295 | spa |
| dcterms.references | Lemasters J.J. (2017). Evolution of voltage-dependent anion channel function: From molecular sieve to governator to actuator of ferroptosis. Front Oncol. 7: 303 | spa |
| dcterms.references | Lemeshko S.V. & Lemeshko V.V. (2000). Metabolically derived potential on the outer membrane of mitochondria: a computational model. Biophys J. 79: 2785-2800 | spa |
| dcterms.references | Lemeshko V.V. (2002). Model of the outer membrane potential generation by the inner membrane of mitochondria. Biophys J. 82: 684-692 | spa |
| dcterms.references | Lemeshko V.V. (2006). Theoretical evaluation of a possible nature of the outer membrane potential of mitochondria. Eur Biophys J. 36: 57-66 | spa |
| dcterms.references | Lemeshko V.V., Haridas V., Quijano Pérez J.C., Gutterman J.U.(2006a). Avicins, natural anticancer saponins, permeabilize mitochondrial membranes. Arch Biochem Biophys. 454(2): 114-122 | spa |
| dcterms.references | Lemeshko V., Guzmán F., Patarroyo M.E., Segura C., Orduz S. (2006b) Synthetic peptide having an ionophoric and antimicrobial activity. United States Patent No. 7041647 | spa |
| dcterms.references | Lemeshko V.V. (2014). VDAC electronics: 1. VDAC-hexo(gluco)kinase generator of the mitochondrial outer membrane potential. Biochim Biophys Acta. 1838: 1362-1371 | spa |
| dcterms.references | Lemeshko V. (2015). The Warburg effect as a VDAC-hexokinase-mediated electrical suppression of mitochondrial energy metabolism. FASEB J. 29 (Suppl 1): 725-27 | spa |
| dcterms.references | Lemeshko V.V. (2016). VDAC electronics: 3. VDAC-creatine kinase-dependent generation of the outer membrane potential in respiring mitochondria. Biochim Biophys Acta.1858 (7 PtA): 1411-1418 | spa |
| dcterms.references | Lemeshko V.V. (2017a). The mitochondrial outer membrane potential as an electrical feedback control of cell energy metabolism. En: T.K. Rostovtseva (Ed.), Molecular Basis for Mitochondrial Signaling, Springer International Publishing, New York, Chapter 9: 217-250 | spa |
| dcterms.references | Lemeshko V.V. (2017b). VDAC electronics: 4. Novel electrical mechanism and thermodynamic estimations of glucose repression of yeast respiration. Biochim Biophys Acta.1859 (11): 2213-2223 | spa |
| dcterms.references | Liu M.Y. & Colombini M. (1992). A soluble mitochondrial protein increases the voltage dependence of the mitochondrial channel, VDAC. J Bioenerg Biomembr. 24: 41-46 | spa |
| dcterms.references | Luttik M.A., Overkamp K.M., Kötter P., de Vries S., van Dijken J.P., Pronk J.T. (1998). The Saccharomyces cerevisiaeNDE1 and NDE2 genes encode separate mitochondrial NADH dehydrogenases catalyzing the oxidation of cytosolic NADH. J Biol Chem. 273 (38): 24529-24534 | spa |
| dcterms.references | Maldonado E.N., Patnaik J., Mullins M.R., Lemasters J.J.(2010). Free tubulin modulates mitochondrial membrane potential in cancer cells. Cancer Res. 70 (24): 10192-10201 | spa |
| dcterms.references | Maldonado E.N., Sheldon K.L., DeHart D.N., Patnaik J., Manevich Y., Townsend D.M., Bezrukov S.M., Rostovtseva T.K., Lemasters J.J. (2013). Voltage-dependent anion channels modulate mitochondria metabolism in cancer cells: Regulation by free tubulin and erastin. J Biol Chem.288 (17): 11920-11929 | spa |
| dcterms.references | Mannella C.A. (1982). Structure of the outer mitochondrial membrane: Ordered arrays of porelike subunits in outer-membrane fractions from Neurospora crassa mitochondria. J Cell Biol. 94: 680-687. | spa |
| dcterms.references | Marín-Hernández A., Rodríguez-Enríquez S., Vital-González P.A., Flores-Rodríguez F.L., Macías-Silva M., Sosa-Garrocho M., Moreno-Sánchez R. (2006). Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an overexpressed but strongly product-inhibited hexokinase. FEBS J. 273 (9): 1975-1988 | spa |
| dcterms.references | Mastrangelo D., Pelosi E., Castelli G., Lo-Coco F., Testa U.(2017). Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation. Blood Cells Mol Dis pii. S1079-9796 (17): 30327-3 | spa |
| dcterms.references | O’Gorman E., Beutner G., Dolder M., Koretsky A.P., Brdiczka D., Wallimann T. (1997). The role of creatine kinase in inhibition of mitochondrial permeability transition. FEBS Lett. 414: 253-257. | spa |
| dcterms.references | Ohnishi T., Kawaguchi K., Hagihara B. (1966). Preparation and some properties of yeast Mitochondria. J Biol Chem. 241(8): 1797-1806 | spa |
| dcterms.references | Orduz S., Lemeshko V. (2016). Péptido sintético policatiónico como agente ionofórico, antimicrobiano, antitumoral e insecticida. Rad. Gaceta 701, No. 174, 31 de julio de 2014, Superintendencia de Industria y Comercio de Colombia. Res. No.: 22123 | spa |
| dcterms.references | Pfeiffer T., Morley A. (2014). An evolutionary perspective on the Crabtree effect. Front Mol Biosci. 1: 17. | spa |
| dcterms.references | Pinz I., Ostroy S.E., Hoyer K., Osinska H., Robbins J., Molkentin J.D., Ingwall J.S. (2008). Calcineurin-induced energy wasting in a transgenic mouse model of heart failure. Am J Physiol Heart Circ Physiol. 294 (3): H1459-H1466 | spa |
| dcterms.references | Porcelli A.M., Ghelli A., Zanna C., Pinton P., Rizzuto R., Rugolo M. (2005). pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant. Biochem Biophys Res Commun. 326: 799-804 | spa |
| dcterms.references | Rigoulet M., Aguilaniu H., Avéret N., Bunoust O., Camougrand N., Grandier-Vazeille X., Larsson C., Pahlman I.L., Manon S., Gustafsson L. (2004). Organization and regulation of the cytosolic NADH metabolism in the yeastSaccharomyces cerevisiae.Mol Cell Biochem. 256-257(1-2): 73-81 | spa |
| dcterms.references | Rizzuto R., De Stefani D., Raffaello A., Mammucari C.(2012). Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 13 (9): 566-578 | spa |
| dcterms.references | Rostovtseva T., Colombini M. (1997). VDAC channels mediate and gate the flow of ATP: Implications for the regulation of mitochondrial function. BiophysJ. 72 (5): 1954-1962. | spa |
| dcterms.references | Rostovtseva T.K., Komarov A., Bezrukov S.M., Colombini M. (2002). Dynamics of nucleotides in VDAC channels: Structure-specific noise generation. Biophys J. 82 (1 Pt 1): 193-205. | spa |
| dcterms.references | Rostovtseva T.K., Bezrukov S.M. (2012). VDAC inhibition by tubulin and its physiological implications. Biochim Biophys Acta. 1818 (6): 1526-1535 | spa |
| dcterms.references | Rostovtseva T.K., Gurnev P.A., Protchenko O., Hoogerheide D.P., Yap T.L., Philpott C.C., Lee J.C., Bezrukov S.M.(2015). α-Synuclein shows high affinity interaction with voltage-dependent anion channel, suggesting mechanisms of mitochondrial regulation and toxicity in Parkinson disease. J Biol Chem. 290 (30):18467-18477. | spa |
| dcterms.references | Rostovtseva T.K., Gurnev P.A., Protchenko O., Hoogerheide D.P., Yap T.L., Philpott C.C., Lee J.C., Bezrukov S.M.(2015). α-Synuclein shows high affinity interaction with voltage-dependent anion channel, suggesting mechanisms of mitochondrial regulation and toxicity in Parkinson disease. J Biol Chem. 290 (30):18467-18477 | spa |
| dcterms.references | Rostovtseva, T.K., Hoogerheide D.P., Rovni A., Bezrukov S.M.(2017). Lipids in regulation of the mitochondrial outer membrane permeability, bioenergetics, and metabolism. In: T.K. Rostovtseva (Ed.), Molecular Basis for Mitochondrial Signaling, Springer International Publishing, New York, Chapter. 8: 185-215 | spa |
| dcterms.references | Saks V., Guzun R., Timohhina N., Tepp K., Varikmaa M., Monge C., Beraud N., Kaambre T., Kuznetsov A., Kadaja L., Eimre M., Seppet E. (2010). Structure–function relation-ships in feedback regulation of energy fluxes in vivo in health and disease: Mitochondrial interactosome. Biochim Biophys Acta. 1797 (6-7): 678-697. | spa |
| dcterms.references | Sen U., Shenoy P.S., Bose B. (2017). Opposing effects of low versus high concentrations of water-soluble vitamins/dietary ingredients vitamin C and niacin on colon cancer stem cells (CSCs). Cell Biol Int. 41 (10): 1127-1145. | spa |
| dcterms.references | Shoshan-Barmatz V., Ben-Hail D., Admoni L., Krelin Y., Tripathi S.S. (2015). The mitochondrial voltage-dependent anion channel 1 in tumor cells. Biochim Biophys Acta.1848 (10 PtB): 2547-2575 | spa |
| dcterms.references | Shoshan-Barmatz V., Krelin Y., Shteinfer-Kuzmine A., Arif T.(2017). Voltage-dependent anion channel 1 as an emerging drug target for novel anti-cancer therapeutics. Front Oncol.7: 154. | spa |
| dcterms.references | Shoshan-Barmatz V., Krelin Y., Shteinfer-Kuzmine A. (2018). VDAC1 functions in Ca2+ homeostasis and cell life and death in health and disease. Cell Calcium. 69: 81-100. | spa |
| dcterms.references | Simson P., Jepihhina N., Laasmaa M., Peterson P., Birkedal R., Vendelin M. (2016). Restricted ADP movement in cardiomyocytes: Cytosolic diffusion obstacles are comple-mented with a small number of open mitochondrial voltage-dependent anion channels. J Mol Cell Cardiol. 97: 197-203. | spa |
| dcterms.references | Timohhina N., Guzun R., Tepp K., Monge C., Varikmaa M., Vija H., Sikk P., Kaambre T., Sackett D., Saks V. (2009). Direct measurement of energy fluxes from mitochondria into cytoplasm in permeabilized cardiac cells in situ: Some evidence for mitochondrial interactosome. J Bioenerg Biomembr. 41: 259-275. | spa |
| dcterms.references | Vander Heiden M.G., Chandel N.S., Li X.X., Schumacker P.T., Colombini M., Thompson C.B. (2000). Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proc Natl Acad Sci USA. 97(9): 4666-4671 | spa |
| dcterms.references | Vazeille X., Larsson C., Pahlman I.L., Manon S., Gustafsson L.(2004) Organization and regulation of the cytosolic NADH metabolism in the yeast Saccharomyces cerevisiae. Mol Cell Biochem. 256-257 (1-2): 73-81. | spa |
| dcterms.references | Wallimann T., Tokarska-Schlattner M., Schlattner U. (2011). The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 40: 1271-1296. | spa |
| dcterms.references | Wilson J.E. (1997). Homologous and heterologous interactions between hexokinase and mitochondrial porin: Evolutionary implications. J Bioenerg Biomembr. 29 (1): 97-102. | spa |
| dcterms.references | Xia J., Xu H., Zhang X., Allamargot C., Coleman K.L., Nessler R., Frech I., Tricot G., Zhan F. (2017). Multiple myeloma tumor cells are selectively killed by pharmacologically-dosed ascorbic acid. EBioMedicine. 18: 41-49. | spa |
| dcterms.references | Zizi M., Forte M., Blachly-Dyson E., Colombini M. (1994). NADH regulates the gating of VDAC, the mitochondrial outer membrane channel. J Biol Chem. 269 (3): 1614-1616. | spa |
| dcterms.references | Zorova L.D., Popkov V.A., Plotnikov E.Y., Silachev D.N., Pevzner I.B., Jankauskas S.S., Babenko V.A., Zorov S.D., Balakireva A.V., Juhaszova M, Sollott S.J., Zorov D.B. (2017). Mitochondrial membrane potential. Anal Biochem pii. S0003-2697 (17): 30293-2. | spa |
| dc.rights.accessrights | info:eu-repo/semantics/openAccess | spa |
| dc.type.driver | info:eu-repo/semantics/article | spa |
| dc.type.version | info:eu-repo/semantics/publishedVersion | spa |
| dc.rights.creativecommons | Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0) | spa |
| dc.identifier.doi | https://doi.org/10.18257/raccefyn.549 | - |
| dc.subject.proposal | Membrana externa mitocondrial | spa |
| dc.subject.proposal | Mitochondrial outer membrane | eng |
| dc.subject.proposal | VDAC | spa |
| dc.subject.proposal | VDAC | eng |
| dc.subject.proposal | Potencial de membrana | spa |
| dc.subject.proposal | Membrane potential | eng |
| dc.subject.proposal | Levadura | spa |
| dc.subject.proposal | Yeast | eng |
| dc.subject.proposal | Cáncer | spa |
| dc.subject.proposal | Cancer | eng |
| dc.subject.proposal | Corazón | spa |
| dc.subject.proposal | Heart | eng |
| dc.type.coar | http://purl.org/coar/resource_type/c_6501 | spa |
| dc.relation.ispartofjournal | Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales | spa |
| dc.relation.citationvolume | 42 | spa |
| dc.relation.citationstartpage | 6 | spa |
| dc.relation.citationendpage | 21 | spa |
| dc.publisher.place | Bogotá, Colombia | spa |
| dc.contributor.corporatename | Academia Colombiana de Ciencias Exactas, Físicas y Naturales | spa |
| dc.relation.citationissue | 162 | spa |
| dc.type.content | DataPaper | spa |
| dc.type.redcol | http://purl.org/redcol/resource_type/ART | spa |
| oaire.accessrights | http://purl.org/coar/access_right/c_abf2 | spa |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 | spa |
| Appears in Collections: | BA. Revista de la Academia Colombiana de Ciencias Exactas Físicas y Naturales | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 1. El papel de la membrana mitocondrial externa en el control del metabolismo energético celular.pdf | Ciencias biomédicas | 1.73 MB | Adobe PDF |  View/Open |
This item is licensed under a Creative Commons License
