Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

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 histoch...

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Bibliographic Details
Published in:The Journal of cell biology 2000-09, Vol.150 (6), p.1283-1297
Main Authors: Milner, Derek J., Mavroidis, Manolis, Weisleder, Noah, Capetanaki, Yassemi
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - pharmacology
Animals
Cardiomyopathies - metabolism
Cell Respiration - physiology
Cells
Cellular biology
Creatine
Cytochromes
Cytoskeleton
Desmin - genetics
Desmin - metabolism
Energy Metabolism - drug effects
Energy Metabolism - physiology
Heart
Intermediate filaments
Intermediate Filaments - metabolism
Intermediate Filaments - ultrastructure
Mice
Mice, Knockout
Microscopy, Electron
Mitochondria
Mitochondria - metabolism
Mitochondria - ultrastructure
Muscle Fibers, Skeletal - metabolism
Muscle Fibers, Skeletal - ultrastructure
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Muscles
Muscular system
Myocardium
Myocardium - cytology
Myocardium - metabolism
Myofibrils
Original
Respiration
Respiratory system
Skeletal muscle
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Summary: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 (Km) 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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.150.6.1283