Original Article

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

Correspondence to: Yassemi Capetanaki, Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030. Tel:(713) 798-4609 Fax:(713) 798-8005

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K_m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle.

Key Words: intermediate filaments, mitochondrial proliferation, cardiomyopathy, respiration, desmin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Panagopoulou, P., Davos, C. H., Milner, D. J., Varela, E., Cameron, J., Mann, D. L., Capetanaki, Y. (2008). Desmin mediates TNF-{alpha}-induced aggregate formation and intercalated disk reorganization in heart failure. J. Cell Biol. 181: 761-775 [Abstract] [Full Text]  
• Konieczny, P., Fuchs, P., Reipert, S., Kunz, W. S., Zeold, A., Fischer, I., Paulin, D., Schroder, R., Wiche, G. (2008). Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. J. Cell Biol. 181: 667-681 [Abstract] [Full Text]  
• Nishi, M., Hu, K., Murray, J. M., Roos, D. S. (2008). Organellar dynamics during the cell cycle of Toxoplasma gondii. J. Cell Sci. 121: 1559-1568 [Abstract] [Full Text]  
• Boateng, S. Y., Goldspink, P. H. (2008). Assembly and maintenance of the sarcomere night and day. Cardiovasc Res 77: 667-675 [Abstract] [Full Text]  
• Kouloumenta, A., Mavroidis, M., Capetanaki, Y. (2007). Proper Perinuclear Localization of the TRIM-like Protein Myospryn Requires Its Binding Partner Desmin. J. Biol. Chem. 282: 35211-35221 [Abstract] [Full Text]  
• Stone, M. R., O'Neill, A., Lovering, R. M., Strong, J., Resneck, W. G., Reed, P. W., Toivola, D. M., Ursitti, J. A., Omary, M. B., Bloch, R. J. (2007). Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization. J. Cell Sci. 120: 3999-4008 [Abstract] [Full Text]  
• Fukui, H., Moraes, C. T. (2007). Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Hum Mol Genet 16: 783-797 [Abstract] [Full Text]  
• Shardonofsky, F. R., Capetanaki, Y., Boriek, A. M. (2006). Desmin modulates lung elastic recoil and airway responsiveness. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L890-L896 [Abstract] [Full Text]  
• Guerrero, K., Wuyam, B., Mezin, P., Vivodtzev, I., Vendelin, M., Borel, J.-C., Hacini, R., Chavanon, O., Imbeaud, S., Saks, V., Pison, C. (2005). Functional coupling of adenine nucleotide translocase and mitochondrial creatine kinase is enhanced after exercise training in lung transplant skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R1144-R1154 [Abstract] [Full Text]  
• van den Bosch, B. J.C., van den Burg, C. M.M., Schoonderwoerd, K., Lindsey, P. J., Scholte, H. R., de Coo, R. F.M., van Rooij, E., Rockman, H. A., Doevendans, P. A., Smeets, H. J.M. (2005). Regional absence of mitochondria causing energy depletion in the myocardium of muscle LIM protein knockout mice. Cardiovasc Res 65: 411-418 [Abstract] [Full Text]  
• Omary, M. B., Coulombe, P. A., McLean, W.H. I. (2004). Intermediate Filament Proteins and Their Associated Diseases. NEJM 351: 2087-2100 [Full Text]  
• Kee, A. J., Schevzov, G., Nair-Shalliker, V., Robinson, C. S., Vrhovski, B., Ghoddusi, M., Qiu, M. R., Lin, J. J.-C., Weinberger, R., Gunning, P. W., Hardeman, E. C. (2004). Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy. J. Cell Biol. 166: 685-696 [Abstract] [Full Text]  
• McElhinny, A. S., Perry, C. N., Witt, C. C., Labeit, S., Gregorio, C. C. (2004). Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in striated muscle development. J. Cell Sci. 117: 3175-3188 [Abstract] [Full Text]  
• Shah, S. B., Davis, J., Weisleder, N., Kostavassili, I., McCulloch, A. D., Ralston, E., Capetanaki, Y., Lieber, R. L. (2004). Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation. Biophys. J 86: 2993-3008 [Abstract] [Full Text]  
• Weisleder, N., Taffet, G. E., Capetanaki, Y. (2004). Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc. Natl. Acad. Sci. USA 101: 769-774 [Abstract] [Full Text]  
• Czubryt, M. P., Olson, E. N. (2004). Balancing Contractility and Energy Production: The Role of Myocyte Enhancer Factor 2 (MEF2) in Cardiac Hypertrophy. Recent Prog Horm Res 59: 105-124 [Abstract] [Full Text]  
• Rezniczek, G. A., Abrahamsberg, C., Fuchs, P., Spazierer, D., Wiche, G. (2003). Plectin 5'-transcript diversity: short alternative sequences determine stability of gene products, initiation of translation and subcellular localization of isoforms. Hum Mol Genet 12: 3181-3194 [Abstract] [Full Text]  
• Wagner, O. I., Lifshitz, J., Janmey, P. A., Linden, M., McIntosh, T. K., Leterrier, J.-F. (2003). Mechanisms of Mitochondria-Neurofilament Interactions. J. Neurosci. 23: 9046-9058 [Abstract] [Full Text]  
• Haubold, K. W., Allen, D. L., Capetanaki, Y., Leinwand, L. A. (2003). Loss of desmin leads to impaired voluntary wheel running and treadmill exercise performance. J. Appl. Physiol. 95: 1617-1622 [Abstract] [Full Text]  
• De Vos, K. J., Sable, J., Miller, K. E., Sheetz, M. P. (2003). Expression of Phosphatidylinositol (4,5) Bisphosphate-specific Pleckstrin Homology Domains Alters Direction But Not the Level of Axonal Transport of Mitochondria. Mol. Biol. Cell 14: 3636-3649 [Abstract] [Full Text]  
• Andrienko, T., Kuznetsov, A. V., Kaambre, T., Usson, Y., Orosco, A., Appaix, F., Tiivel, T., Sikk, P., Vendelin, M., Margreiter, R., Saks, V. A. (2003). Metabolic consequences of functional complexes of mitochondria, myofibrils and sarcoplasmic reticulum in muscle cells. J. Exp. Biol. 206: 2059-2072 [Abstract] [Full Text]  
• Saks, V., Kuznetsov, A., Andrienko, T., Usson, Y., Appaix, F., Guerrero, K., Kaambre, T., Sikk, P., Lemba, M., Vendelin, M. (2003). Heterogeneity of ADP Diffusion and Regulation of Respiration in Cardiac Cells. Biophys. J 84: 3436-3456 [Abstract] [Full Text]  
• Schroder, R., Goudeau, B., Simon, M. C., Fischer, D., Eggermann, T., Clemen, C. S., Li, Z., Reimann, J., Xue, Z., Rudnik-Schoneborn, S., Zerres, K., van der Ven, P. F. M., Furst, D. O., Kunz, W. S., Vicart, P. (2003). On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria. Hum Mol Genet 12: 657-669 [Abstract] [Full Text]  
• Chen, F., Chang, R., Trivedi, M., Capetanaki, Y., Cryns, V. L. (2003). Caspase Proteolysis of Desmin Produces a Dominant-negative Inhibitor of Intermediate Filaments and Promotes Apoptosis. J. Biol. Chem. 278: 6848-6853 [Abstract] [Full Text]  
• Mavroidis, M., Capetanaki, Y. (2002). Extensive Induction of Important Mediators of Fibrosis and Dystrophic Calcification in Desmin-Deficient Cardiomyopathy. Am. J. Pathol. 160: 943-952 [Abstract] [Full Text]  
• Shah, S. B., Su, F.-C., Jordan, K., Milner, D. J., Friden, J., Capetanaki, Y., Lieber, R. L. (2002). Evidence for increased myofibrillar mobility in desmin-null mouse skeletal muscle. J. Exp. Biol. 205: 321-325 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents