Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence

P.J. Coates, R. Nenutil, A. McGregor, S.M. Picksley, D.H. Crouch, P.A. Hall, E.G. Wright

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    153 Citations (Scopus)

    Abstract

    The two prohibitin proteins, Phblp and Phb2pBAB37, have been ascribed various functions, including cell cycle regulation, apoptosis, assembly of mitochondrial respiratory chain enzymes, and aging. We show that the mammalian prohibitins are present in the inner mitochondrial membrane and are always bound to each other, with no free protein detectable. They are coexpressed during development and in adult mammalian tissues, and expression levels are indicative of a role in mitochondrial metabolism, but are not compatible with roles in the regulation of cellular proliferation or apoptosis. High level expression of the proteins is consistently seen in primary human tumors, while cellular senescence of human and chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The two proteins are induced by metabolic stress caused by an imbalance in the synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do not respond to oxidative stress, heat shock, or other cellular stresses. The gene promoter sequences contain binding sites for the Myc oncoprotein and overexpression of Myc induces expression of the prohibitins. The data support conserved roles for the prohibitins in regulating mitochondrial respiratory activity and in aging.

    Original languageEnglish
    Pages (from-to)262-273
    Number of pages12
    JournalExperimental Cell Research
    Volume265
    Issue number2
    DOIs
    Publication statusPublished - 1 May 2001

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  • Cite this

    Coates, P. J., Nenutil, R., McGregor, A., Picksley, S. M., Crouch, D. H., Hall, P. A., & Wright, E. G. (2001). Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Experimental Cell Research, 265(2), 262-273. https://doi.org/10.1006/excr.2001.5166