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Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear

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Abstract

The Mpv17 gene encodes a mitochondrial inner-membrane protein that has been implicated in the metabolism of reactive oxygen species. The loss of function in Mpv17-/- mice leads to early sensorineural deafness associated with severe inner ear degeneration and late onset of kidney failure. The present study demonstrates that the onset of the degeneration of the cochlear neuroepithelia is related to the onset of auditory function and appears to be first restricted to the outer hair cells (OHC), which subsequently undergo rapid degeneration. At the age of 18 days, the OHC lateral membrane degenerates and extensive vacuolization of the cytoplasm is followed by lysis of the OHCs. Such degenerative processes have been seen for the first time in relation to auditory dysfunction. The structural degeneration pattern of the OHC appears to be similar to the described paraptotic processes (an alternative form of programmed cell death) discussed in the literature as a cause of cytoplasmic neurodegeneration. In contrast, the melanocyte-like intermediate cells that are of neural crest origin and that are located in the stria vascularis, undergo apoptosis, as documented ultrastructurally. A lack of Mpv17 protein function in mitochondria thus seems to initiate tissue-specific cell-death pathways resulting in the pathology seen during the degeneration process.

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Abbreviations

ABR:

Auditory brainstem responses

BC:

Basal cell

IHC:

Inner hair cell

IMC:

Intermediate cell

MC:

Marginal cell

mtDNA:

Mitochondrial DNA

OHC:

Outer hair cell

ROS:

Radical oxygen species

SGC:

Spiral ganglion cell

SV:

Stria vascularis

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Acknowledgments

The authors thank Dr. Heidi Felix (Zürich) for long-term support and cooperation, Prof. Dr. H. Weiher for critical reading of the manuscript, Mrs. V. Hoffmann and J. Nievergelt (Zürich) and U. Becker-Lendzian (Düsseldorf) for their excellent technical assistance and Dr. Marc Pearson (Neuss) and Dr. Klara Trcka (Düsseldorf) for editorial help.

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Authors and Affiliations

  1. Research Laboratory, Department of Otorhinolaryngology, No. 23.12, Heinrich-Heine-University Düsseldorf, Medical Faculty, Universitätsstrasse 1, 40225, Düsseldorf, Germany

    Angela-Maria Meyer zum Gottesberge

  2. Department of Otorhinolaryngology, Division of Phoniatrics and Pediatric Audiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Thomas Massing

  3. Department of Otorhinolaryngology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Stefan Hansen

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  1. Angela-Maria Meyer zum Gottesberge
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Correspondence to Angela-Maria Meyer zum Gottesberge.

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Meyer zum Gottesberge, AM., Massing, T. & Hansen, S. Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear. Cell Tissue Res 347, 343–356 (2012). https://doi.org/10.1007/s00441-012-1326-7

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