Research Article
No access
Published Online: 7 November 2005

Spontaneously Immortalized Mouse Embryo Fibroblasts: Growth Behavior of Wild-Type and Vimentin-Deficient Cells in Relation to Mitochondrial Structure and Activity

Publication: DNA and Cell Biology
Volume 24, Issue Number 11


Dependent on the presence or absence of vimentin, primary mouse embryo fibroblasts exhibit different growth characteristics in vitro. While most Vim+/+ fibroblasts stop dividing and die via apoptosis, a substantial fraction of cells immortalize and proliferate almost normally. Vim−/− fibroblasts cease to divide earlier, immortalize in vanishingly small numbers and thereafter proliferate extremely slowly. Early after immortalization, Vim+/+ imm fibroblasts appear structurally almost normal, whereas Vim−/− imm fibroblasts equal postmitotic "crisis" cells, which are characterized by increased cell size, altered cell ultrastructure, nuclear enlargement, genome destabilization, structural degeneration of mitochondria, and diminution of mitochondrial respiratory activity. The differences between immortalized Vim+/+ imm and Vim−/− imm fibroblasts persist during early cell cloning but disappear during serial subcultivation. At high cell passage, cloned, immortalized vim fibroblasts grow nearly as fast as their cloned vim+ counterparts, and also resemble them in size, ultrastructure, nuclear volume, and mitochondrial complement; they very likely employ redundancy to cope with the loss of vimentin function when adjusting structure and behavior to that of immortalized vim+ fibroblasts. Reduction in nuclear size occurs via release of large amounts of filamentous chromatin into extracellular space; because it is complexed with extracellular matrix proteins, it tends to form clusters and to tightly stick to the surface of other cells, thus providing a potential for horizontal gene transfer. On the other hand, cloned vim+ and vim fibroblasts are equal in showing contact inhibition at young age and becoming anchorage-independent during serial subcultivation, as indicated by the formation of multilayered and -faceted cell sheets and huge spheroids on top of or in soft agar. With this, immortalized vim fibroblasts reduce their adhesiveness to the substratum which, in their precrisis state and early after cloning, is much higher than that of their vim+ counterparts. In addition, the coupling between the mitochondrial respiratory chain and oxidative phosphorylation is stronger in vim+ than vim fibroblasts. It appears from these data that after explantation of fibroblasts from the mouse embryo the primary cause of cell and mitochondrial degeneration, including genomic instability, is the mitochondrial production of reactive oxygen species in a vicious circle, and that vimentin provides partial protection from oxidative damage. As a matrix protein with specific in vitro and in vivo affinities for nuclear and mitochondrial, recombinogenic DNA, it may exert this effect preferentially at the genome level via its influence on recombination and repair processes, and in this way also assist the cells in immortalizing. Additional protection of mitochondria by vimentin may occur at the level of mitochondrial fatty acid metabolism.

Get full access to this article

View all available purchase options and get full access to this article.

Information & Authors


Published In

cover image DNA and Cell Biology
DNA and Cell Biology
Volume 24Issue Number 11November 2005
Pages: 680 - 709
PubMed: 16274292


Published online: 7 November 2005
Published in print: November 2005


Request permissions for this article.




    Genrich V. Tolstonog
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Heinrich-Pette Institute for Experimental Virology and Immunology, Hamburg University, Hamburg, Germany.
    Irina V. Belichenko-Weitzmann
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Northern Community College, Science Division, Norfolk, Nebraska.
    Jian-Ping Lu
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Department of Pathology, Conway Institute of Biomolecular and Biomedical Research, University College, Dublin, Ireland.
    Roland Hartig
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Institut für Immunologie, Medizinische Fakultät, Otto-von Guericke-Universität Magdeburg, Magdeburg, Germany.
    Robert L. Shoeman
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Max-Planck-Institut für Medizinische Forschung, Heidelberg, Germany.
    Ulrike Taub
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Peter Traub
    Max-Planck-Institut für Zellbiologie, Rosenhof, Ladenburg, Germany.
    Present address: Institute for Cellular and Molecular Botany, Bonn University, Bonn, Germany.

    Metrics & Citations



    Export citation

    Select the format you want to export the citations of this publication.

    View Options

    Get Access

    Access content

    To read the fulltext, please use one of the options below to sign in or purchase access.

    Society Access

    If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

    Restore your content access

    Enter your email address to restore your content access:

    Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

    View options


    View PDF/ePub







    Copy the content Link

    Share on social media

    Back to Top