nach oben

Journal of Inherited Metabolic Disease

Erschienen in:

01.07.2012 | SSIEM Symposium 2010

Mitochondrial proteomics—a tool for the study of metabolic disorders

verfasst von: Niels Gregersen, Jakob Hansen, Johan Palmfeldt

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

Mitochondria are important for a number of life and death processes, such as energy production, creation of reactive oxygen species, and elicitation of stress responses. These responses range from induction of protein quality control and antioxidant systems to mitochondria elimination and cell death. Mitochondrial dysfunctions are involved in pathologies associated with many diseases, for example metabolic disorders, diabetes, cancers, cardiovascular and neurodegenerative diseases as well as obesity and aging. Mitochondrial proteomics can be a powerful tool in the study of these diseases, especially since it can cover mitochondrial proteins from several metabolic pathways, such as the citric acid cycle, fatty acid oxidation, and respiratory chain, as well as protein networks involved in stress responses. The mitochondrial proteome can consist of more than 1,000 different proteins. However, it is difficult to define the precise number, since mitochondria are dynamic and difficult to purify, and because an unknown number of proteins possess dual or multiple localization, depending on cell type and physiological conditions. This review describes several quantitative studies of proteins from mitochondria isolated by centrifugation, separated by various methods (e.g., electrophoresis and nanoLC), and analyzed by advanced mass spectrometry. We illustrate the methods by showing that multiple pathways and networks are affected in cells from patients carrying gene variations affecting a mitochondrial protein. The study of cultured skin fibroblasts from patients with ethylmalonic aciduria associated with variations in the genes coding for short-chain acyl-CoA dehydrogenase (SCAD) or ETHE1 are two of the examples. The possibility of obtaining mitochondrial proteomics data from whole cell proteomics studies is also exemplified by the involvement of liver mitochondria in metabolic syndrome.

Web-based mitochondrial proteome databases:

http://mitominer.mrc-mbu.cam.ac.uk/release-1.1/begin.do

http://www.mitop.de:8080/mitop2/

http://www.mitoproteome.org/

Andersen JS, Mann M (2006) Organellar proteomics: turning inventories into insights. EMBO Rep 7:874–879PubMedCrossRef

Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29PubMedCrossRef

Baiges I, Palmfeldt J, Blade C, Gregersen N, Arola L (2010) Lipogenesis is decreased by grape seed proanthocyanidins according to liver proteomics of rats fed a high fat diet. Mol Cell Proteomics 9:1499–1513PubMedCrossRef

Bereiter-Hahn J, Voth M, Mai S, Jendrach M (2008) Structural implications of mitochondrial dynamics. Biotechnol J 3:765–780PubMedCrossRef

Bi X, Lin Q, Foo TW et al (2006) Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways: mechanism of tumorigenesis. Mol Cell Proteomics 5:1119–1130PubMedCrossRef

Brandon M, Baldi P, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25:4647–4662PubMedCrossRef

Broadwater L, Pandit A, Clements R et al (2011) Analysis of the mitochondrial proteome in multiple sclerosis cortex. Biochim Biophys Acta 1812:630–641PubMedCrossRef

Bross P, Naundrup S, Hansen J et al (2008) The Hsp60-(p.V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo. J Biol Chem 283:15694–15700PubMedCrossRef

Bross P, Palmfeldt J, Hansen J, Vang S, Gregersen N (2010) Measuring consequences of protein misfolding and cellular stress using OMICS techniques. Methods Mol Biol 648:119–135PubMedCrossRef

Bross P, Frederiksen JB, Bie AS et al (2011) Heterozygosity for an in-frame deletion causes glutaryl-CoA dehydrogenase deficiency in a patient detected by newborn screening: investigation of the effect of the mutant allele. J Inherit Metab Dis (in press)

Bugger H, Chen D, Riehle C et al (2009) Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 58:1986–1997PubMedCrossRef

Chen J, Shi X, Padmanabhan R et al (2008) Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster. Genome Res 18:123–136PubMedCrossRef

Chen X, Li J, Hou J, Xie Z, Yang F (2010) Mammalian mitochondrial proteomics: insights into mitochondrial functions and mitochondria-related diseases. Expert Rev Proteomics 7:333–345PubMedCrossRef

Choudhary C, Kumar C, Gnad F et al (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840PubMedCrossRef

Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762PubMedCrossRef

Collins MO, Choudhary JS (2008) Mapping multiprotein complexes by affinity purification and mass spectrometry. Curr Opin Biotechnol 19:324–330PubMedCrossRef

Cox J, Matic I, Hilger M et al (2009) A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat Protoc 4:698–705PubMedCrossRef

Dedkova EN, Ji X, Lipsius SL, Blatter LA (2004) Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells. Am J Physiol Cell Physiol 286:C406–415PubMedCrossRef

Domon B, Aebersold R (2010) Options and considerations when selecting a quantitative proteomics strategy. Nat Biotechnol 28:710–721PubMedCrossRef

Drousiotou A, DiMeo I, Mineri R, Georgiou T, Stylianidou G, Tiranti V (2011) Ethylmalonic encephalopathy: application of improved biochemical and molecular diagnostic approaches. Clin Genet 79:385–390PubMedCrossRef

Eaton S (2002) Control of mitochondrial beta-oxidation flux. Prog Lipid Res 41:197–239PubMedCrossRef

Ewing RM, Chu P, Elisma F et al (2007) Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol 3:89PubMedCrossRef

Felk S, Ohrt S, Kussmaul L, Storch A, Gillardon F (2010) Activation of the mitochondrial protein quality control system and actin cytoskeletal alterations in cells harbouring the MELAS mitochondrial DNA mutation. J Neurol Sci 295:46–52PubMedCrossRef

Fratelli M, Demol H, Puype M et al (2002) Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc Natl Acad Sci USA 99:3505–3510PubMedCrossRef

Gianazza E, Vergani L, Wait R et al (2006) Coordinated and reversible reduction of enzymes involved in terminal oxidative metabolism in skeletal muscle mitochondria from a riboflavin-responsive, multiple acyl-CoA dehydrogenase deficiency patient. Electrophoresis 27:1182–1198PubMedCrossRef

Gianazza E, Eberini I, Sensi C, Barile M, Vergani L, Vanoni MA (2011) Energy matters: mitochondrial proteomics for biomedicine. Proteomics 11:657–674PubMedCrossRef

Gnad F, Forner F, Zielinska DF, Birney E, Gunawardena J, Mann M (2010) Evolutionary constraints of phosphorylation in eukaryotes, prokaryotes, and mitochondria. Mol Cell Proteomics 9:2642–2653PubMedCrossRef

Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13:589–598PubMedCrossRef

Gregersen N, Bross P (2010) Protein misfolding and cellular stress: an overview. Methods Mol Biol 648:3–23PubMedCrossRef

Gregersen N, Olsen RK (2010) Disease mechanisms and protein structures in fatty acid oxidation defects. J Inherit Metab Dis 33:547–553PubMedCrossRef

Gregersen N, Bross P, Vang S, Christensen JH (2006) Protein misfolding and Human disease. Annu Rev Genomics Hum Genet 7:103–124PubMedCrossRef

Gregersen N, Andresen BS, Pedersen CB, Olsen RK, Corydon TJ, Bross P (2008) Mitochondrial fatty acid oxidation defects–remaining challenges. J Inherit Metab Dis 31:643–657PubMedCrossRef

Hansen J, Corydon TJ, Palmfeldt J et al (2008) Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13). Neuroscience 153:474–482PubMedCrossRef

Hansen J, Palmfeldt J, Vang S, Corydon TJ, Gregersen N, Bross P (2011) Quantitative proteomics reveals cellular targets of celastrol. PLoS One 6:e26634PubMedCrossRef

Hekimi S, Lapointe J, Wen Y (2011) Taking a "good" look at free radicals in the aging process. Trends Cell Biol 21:569–576PubMedCrossRef

Hildebrandt TM, Grieshaber MK (2008) Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria. FEBS J 275:3352–3361PubMedCrossRef

Hirschey MD, Shimazu T, Goetzman E et al (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–125PubMedCrossRef

Honda S, Hirose S (2003) Stage-specific enhanced expression of mitochondrial fusion and fission factors during spermatogenesis in rat testis. Biochem Biophys Res Commun 311:424–432PubMedCrossRef

Hua G, Zhang Q, Fan Z (2007) Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. J Biol Chem 282:20553–20560PubMedCrossRef

Kanehisa M, Araki M, Goto S et al (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36:D480–484PubMedCrossRef

Kim N, Lee Y, Kim H et al (2006a) Potential biomarkers for ischemic heart damage identified in mitochondrial proteins by comparative proteomics. Proteomics 6:1237–1249PubMedCrossRef

Kim SC, Sprung R, Chen Y et al (2006b) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23:607–618PubMedCrossRef

Kim JA, Wei Y, Sowers JR (2008) Role of mitochondrial dysfunction in insulin resistance. Circ Res 102:401–414PubMedCrossRef

Kocher T, Superti-Furga G (2007) Mass spectrometry-based functional proteomics: from molecular machines to protein networks. Nat Methods 4:807–815PubMedCrossRef

Landriscina M, Maddalena F, Laudiero G, Esposito F (2009) Adaptation to oxidative stress, chemoresistance, and cell survival. Antioxid Redox Signal 11:2701–2716PubMedCrossRef

Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157PubMedCrossRef

Lyamzaev KG, Nepryakhina OK, Saprunova VB et al (2008) Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): formation of mitoptotic bodies and extrusion of mitochondrial material from the cell. Biochim Biophys Acta 1777:817–825PubMedCrossRef

Madian AG, Regnier FE (2010) Proteomic identification of carbonylated proteins and their oxidation sites. J Proteome Res 9:3766–3780PubMedCrossRef

McDonagh B, Ogueta S, Lasarte G, Padilla CA, Barcena JA (2009) Shotgun redox proteomics identifies specifically modified cysteines in key metabolic enzymes under oxidative stress in Saccharomyces cerevisiae. J Proteomics 72:677–689PubMedCrossRef

Meisinger C, Sickmann A, Pfanner N (2008) The mitochondrial proteome: from inventory to function. Cell 134:22–24PubMedCrossRef

Mueller JC, Andreoli C, Prokisch H, Meitinger T (2004) Mechanisms for multiple intracellular localization of human mitochondrial proteins. Mitochondrion 3:315–325PubMedCrossRef

Neilson KA, Ali NA, Muralidharan S et al (2011) Less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics 11:535–553PubMedCrossRef

Nilsson T, Mann M, Aebersold R, Yates JR 3rd, Bairoch A, Bergeron JJ (2010) Mass spectrometry in high-throughput proteomics: ready for the big time. Nat Methods 7:681–685PubMedCrossRef

Olsen RK, Olpin SE, Andresen BS et al (2007) ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 130:2045–2054PubMedCrossRef

Ong SE, Mann M (2006) A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC). Nat Protoc 1:2650–2660PubMedCrossRef

Pagliarini DJ, Calvo SE, Chang B et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–123PubMedCrossRef

Palmfeldt J, Vang S, Stenbroen V et al (2009) Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress. Proteome Sci 7:20PubMedCrossRef

Palmfeldt J, Vang S, Stenbroen V et al (2011) Proteomics reveals that redox regulation is disrupted in patients with ethylmalonic encephalopathy. J Proteome Res 10:2389–2396PubMedCrossRef

Pedersen CB, Kolvraa S, Kolvraa A et al (2008) The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level. Hum Genet 124:43–56PubMedCrossRef

Pedersen CB, Zolkipli Z, Vang S et al (2010) Antioxidant dysfunction: potential risk for neurotoxicity in ethylmalonic aciduria. J Inherit Metab Dis 33:211–222PubMedCrossRef

Perkins DN, Pappin DJ, Creasy DM, Cottrell JS (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20:3551–3567PubMedCrossRef

Piantadosi CA (2011) Regulation of mitochondrial processes by protein S-nitrosylation. Biochim Biophys Acta. doi:10.1016/j.bbagen.2011.03.008

Pieczenik SR, Neustadt J (2007) Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83:84–92PubMedCrossRef

Pienaar IS, Dexter DT, Burkhard PR (2010) Mitochondrial proteomics as a selective tool for unraveling Parkinson's disease pathogenesis. Expert Rev Proteomics 7:205–226PubMedCrossRef

Priault M, Salin B, Schaeffer J, Vallette FM, di Rago JP, Martinou JC (2005) Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 12:1613–1621PubMedCrossRef

Prokisch H, Andreoli C, Ahting U et al (2006) MitoP2: the mitochondrial proteome database–now including mouse data. Nucleic Acids Res 34:D705–711PubMedCrossRef

Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839PubMedCrossRef

Rabilloud T, Strub JM, Carte N et al (2002) Comparative proteomics as a new tool for exploring human mitochondrial tRNA disorders. Biochemistry 41:144–150PubMedCrossRef

Reifschneider NH, Goto S, Nakamoto H et al (2006) Defining the mitochondrial proteomes from five rat organs in a physiologically significant context using 2D blue-native/SDS-PAGE. J Proteome Res 5:1117–1132PubMedCrossRef

Richard E, Monteoliva L, Juarez S et al (2006) Quantitative analysis of mitochondrial protein expression in methylmalonic acidemia by two-dimensional difference gel electrophoresis. J Proteome Res 5:1602–1610PubMedCrossRef

Rocha H, Ferreira R, Carvalho J et al (2011) Characterization of mitochondrial proteome in a severe case of ETF-QO deficiency. J Proteomics 75:221–228PubMedCrossRef

Ross PL, Huang YN, Marchese JN et al (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3:1154–1169PubMedCrossRef

Schmidt SP, Corydon TJ, Pedersen CB, Bross P, Gregersen N (2010) Misfolding of short-chain acyl-CoA dehydrogenase leads to mitochondrial fission and oxidative stress. Mol Genet Metab 100:155–162PubMedCrossRef

Schmidt SP, Corydon TJ, Pedersen CB et al (2011) Toxic response caused by a misfolding variant of the mitochondrial protein short-chain acyl-CoA dehydrogenase. J Inherit Metab Dis 34:465–475PubMedCrossRef

Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E (2006) Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci USA 103:10224–10229PubMedCrossRef

Selak MA, Lyver E, Micklow E et al (2011) Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function. Mitochondrion 11:342–350PubMedCrossRef

Selbach M, Mann M (2006) Protein interaction screening by quantitative immunoprecipitation combined with knockdown (QUICK). Nat Methods 3:981–983PubMedCrossRef

Sheehan D, McDonagh B, Barcena JA (2010) Redox proteomics. Expert Rev Proteomics 7:1–4PubMedCrossRef

Smeitink JA, Zeviani M, Turnbull DM, Jacobs HT (2006) Mitochondrial medicine: a metabolic perspective on the pathology of oxidative phosphorylation disorders. Cell Metab 3:9–13PubMedCrossRef

Smith AC, Robinson AJ (2009) MitoMiner, an integrated database for the storage and analysis of mitochondrial proteomics data. Mol Cell Proteomics 8:1324–1337PubMedCrossRef

Song HY, Dunbar JD, Zhang YX, Guo D, Donner DB (1995) Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. J Biol Chem 270:3574–3581PubMedCrossRef

St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD (2002) Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277:44784–44790PubMedCrossRef

Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E (2007) Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport. Circ Res 101:1155–1163PubMedCrossRef

Sutak R, Xu X, Whitnall M, Kashem MA, Vyoral D, Richardson DR (2008) Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism. Proteomics 8:1731–1741PubMedCrossRef

Suter B, Kittanakom S, Stagljar I (2008) Interactive proteomics: what lies ahead? Biotechniques 44:681–691PubMedCrossRef

Tang X, Bruce JE (2010) A new cross-linking strategy: protein interaction reporter (PIR) technology for protein-protein interaction studies. Mol Biosyst 6:939–947PubMedCrossRef

Taylor SW, Fahy E, Zhang B et al (2003) Characterization of the human heart mitochondrial proteome. Nat Biotechnol 21:281–286PubMedCrossRef

Tein I, Elpeleg O, Ben-Zeev B et al (2008) Short-chain acyl-CoA dehydrogenase gene mutation (c.319C > T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin. Mol Genet Metab 93:179–189PubMedCrossRef

Tiranti V, D'Adamo P, Briem E et al (2004) Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet 74:239–252PubMedCrossRef

Tiranti V, Viscomi C, Hildebrandt T et al (2009) Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat Med 15:200–205PubMedCrossRef

Trougakos IP, Gonos ES (2009) Chapter 9: Oxidative stress in malignant progression: the role of Clusterin, a sensitive cellular biosensor of free radicals. Adv Cancer Res 104:171–210PubMedCrossRef

Unwin RD, Craven RA, Harnden P et al (2003) Proteomic changes in renal cancer and co-ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect. Proteomics 3:1620–1632PubMedCrossRef

van Maldegem BT, Duran M, Wanders RJ et al (2006) Clinical, biochemical, and genetic heterogeneity in short-chain acyl-coenzyme A dehydrogenase deficiency. JAMA 296:943–952PubMedCrossRef

Waisbren SE, Levy HL, Noble M et al (2008) Short-chain acyl-CoA dehydrogenase (SCAD) deficiency: an examination of the medical and neurodevelopmental characteristics of 14 cases identified through newborn screening or clinical symptoms. Mol Genet Metab 95:39–45PubMedCrossRef

Wang Y, Mohsen AW, Mihalik SJ, Goetzman ES, Vockley J (2010) Evidence for physical association of mitochondrial fatty acid oxidation and oxidative phosphorylation complexes. J Biol Chem 285:29834–29841PubMedCrossRef

Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270PubMed

Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356:1736–1741PubMedCrossRef

Yang L, Vaitheesvaran B, Hartil K et al (2011) The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching. J Proteome Res 10:4134–4149PubMedCrossRef

Ye J, Zhang X, Young C et al (2010) Optimized IMAC-IMAC protocol for phosphopeptide recovery from complex biological samples. J Proteome Res 9:3561–3573PubMedCrossRef

Yogev O, Pines O (2011) Dual targeting of mitochondrial proteins: mechanism, regulation and function. Biochim Biophys Acta 1808:1012–1020PubMedCrossRef

Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ (2010) Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 24:1507–1518PubMedCrossRef

Zhao X, Leon IR, Bak S et al (2011) Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes. Mol Cell Proteomics 10:M110–000299

Zhong N, Xu J (2008) Synergistic activation of the human MnSOD promoter by DJ-1 and PGC-1alpha: regulation by SUMOylation and oxidation. Hum Mol Genet 17:3357–3367PubMedCrossRef

Zlatic SA, Ryder PV, Salazar G, Faundez V (2010) Isolation of labile multi-protein complexes by in vivo controlled cellular cross-linking and immuno-magnetic affinity chromatography. J Vis Exp. doi:10.3791/1855

Zolkipli Z, Pedersen CB, Lamhonwah AM, Gregersen N, Tein I (2011) Vulnerability to oxidative stress in vitro in pathophysiology of mitochondrial short-chain acyl-CoA dehydrogenase deficiency: response to antioxidants. PLoS One 6:e17534PubMedCrossRef

Titel: Mitochondrial proteomics—a tool for the study of metabolic disorders
verfasst von: Niels Gregersen
Jakob Hansen
Johan Palmfeldt
Publikationsdatum: 01.07.2012
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 4/2012
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-012-9480-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

11.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Im Battle of Experts traten zwei Experten auf dem Diabeteskongress gegeneinander an: Die eine vertrat die Auffassung „Sport statt Spritze“ bei Adipositas und Typ-2-Diabetes, der andere forderte „Spritze statt Sport!“ Am Ende waren sie sich aber einig: Die Kombination aus beidem erzielt die besten Ergebnisse.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Mitochondrial proteomics—a tool for the study of metabolic disorders

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Update Innere Medizin

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2012

Newborn screening for lysosomal storage diseases: an ethical and policy analysis

Progress in understanding 2-hydroxyglutaric acidurias

In search of proof-of-concept: gene therapy for glycogen storage disease type Ia

Update and new concepts in vitamin responsive disorders of folate transport and metabolism

Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1 - From blood spot to screening result

The clinical implementation of whole genome sequencing: a conversation with seven scientific experts

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

Vorsicht, erhöhte Blutungsgefahr nach PCI!

Triglyzeridsenker schützt nicht nur Hochrisikopatienten

Gibt es eine Wende bei den bioresorbierbaren Gefäßstützen?

Update Innere Medizin