PuSH - Publikationsserver des Helmholtz Zentrums München: Loss of mitochondrial peptidase <em>Clpp</em> leads to infertility, hearing loss plus growth retardation<em> via</em> accumulation of CLPX, mtDNA, and inflammatory factors.

Navigation

Startseite

English

Recherche

Erweiterte Suche

Durchblättern nach ...

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Erscheinungsjahr

Publikationen im Überblick

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Gispert, S.* ; Parganlija, D.* ; Klinkenberg, M.* ; Dröse, S.* ; Wittig, I.* ; Mittelbronn, M.* ; Grzmil, P.* ; Koob, S.* ; Hamann, A.* ; Walter, M.* ; Buchel, F.* ; Adler, T. ; Hrabě de Angelis, M. ; Busch, D.H.* ; Zell, A.* ; Reichert, A.S.* ; Brandt, U.* ; Osiewacz, H.D.* ; Jendrach, M.* ; Auburger, G.*

Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA, and inflammatory factors.

Hum. Mol. Genet. 22, 4871-4887 (2013)

DOI

PMC

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

Abstract
Metriken
Zusatzinfos

The peptidase CLPP is conserved from bacteria to humans. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder together with the chaperone CLPX. In spite of a known relevance for the mitochondrial unfolded protein response, its substrates and tissue-specific roles are unclear in mammals. Recessive CLPP mutations were recently observed in the human Perrault variant of ovarian failure and sensorineural hearing loss. Here, a first characterization of Clpp null mice demonstrated complete female and male infertility and auditory deficits. Disrupted spermatogenesis already at the spermatid stage and ovarian follicular differentiation failure were evident. Reduced pre-/post-natal survival and marked ubiquitous growth retardation contrasted with only light impairment of movement and respiratory activities. Interestingly, the mice showed resistance to ulcerative dermatitis. Systematic expression studies detected up-regulation of other mitochondrial chaperones, accumulation of CLPX and mtDNA as well as inflammatory factors throughout tissues. T-lymphocytes in the spleen were activated. Thus, murine Clpp deletion represents a faithful Perrault model. The disease mechanism probably involves deficient clearance of mitochondrial components and inflammatory tissue destruction.

Altmetric

Weitere Metriken?

[➜Einloggen]