Universität zu Köln

Winter, Lilli ORCID: 0000-0002-6368-1160, Wittig, Ilka, Peeva, Viktoriya, Eggers, Britta ORCID: 0000-0002-6553-4631, Heidler, Juliana, Chevessier, Frederic, Kley, Rudolf A., Barkovits, Katalin, Strecker, Valentina, Berwanger, Carolin, Herrmann, Harald, Marcus, Katrin, Kornblum, Cornelia, Kunz, Wolfram S. ORCID: 0000-0003-1113-3493, Schroeder, Rolf and Clemen, Christoph S. (2016). Mutant desmin substantially perturbs mitochondrial morphology, function and maintenance in skeletal muscle tissue. Acta Neuropathol., 132 (3). S. 453 - 474. NEW YORK: SPRINGER. ISSN 1432-0533

Full text not available from this repository.

Abstract

Secondary mitochondrial dysfunction is a feature in a wide variety of human protein aggregate diseases caused by mutations in different proteins, both in the central nervous system and in striated muscle. The functional relationship between the expression of a mutated protein and mitochondrial dysfunction is largely unknown. In particular, the mechanism how this dysfunction drives the disease process is still elusive. To address this issue for protein aggregate myopathies, we performed a comprehensive, multi-level analysis of mitochondrial pathology in skeletal muscles of human patients with mutations in the intermediate filament protein desmin and in muscles of hetero- and homozygous knock-in mice carrying the R349P desmin mutation. We demonstrate that the expression of mutant desmin causes disruption of the extrasarcomeric desmin cytoskeleton and extensive mitochondrial abnormalities regarding subcellular distribution, number and shape. At the molecular level, we uncovered changes in the abundancy and assembly of the respiratory chain complexes and supercomplexes. In addition, we revealed a marked reduction of mtDNA- and nuclear DNA-encoded mitochondrial proteins in parallel with large-scale deletions in mtDNA and reduced mtDNA copy numbers. Hence, our data demonstrate that the expression of mutant desmin causes multi-level damage of mitochondria already in early stages of desminopathies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Winter, Lilli UNSPECIFIED orcid.org/0000-0002-6368-1160 UNSPECIFIED Wittig, Ilka UNSPECIFIED UNSPECIFIED UNSPECIFIED Peeva, Viktoriya UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggers, Britta UNSPECIFIED orcid.org/0000-0002-6553-4631 UNSPECIFIED Heidler, Juliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Chevessier, Frederic UNSPECIFIED UNSPECIFIED UNSPECIFIED Kley, Rudolf A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barkovits, Katalin UNSPECIFIED UNSPECIFIED UNSPECIFIED Strecker, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Berwanger, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcus, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornblum, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kunz, Wolfram S. UNSPECIFIED orcid.org/0000-0003-1113-3493 UNSPECIFIED Schroeder, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-265298
DOI:	10.1007/s00401-016-1592-7
Journal or Publication Title:	Acta Neuropathol.
Volume:	132
Number:	3
Page Range:	S. 453 - 474
Date:	2016
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0533
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPIDERMOLYSIS-BULLOSA SIMPLEX; BLUE NATIVE ELECTROPHORESIS; MICE LACKING DESMIN; MUSCULAR-DYSTROPHY; COMPLEX-I; NEURODEGENERATIVE DISEASES; OXIDATIVE-PHOSPHORYLATION; PROTEIN COMPLEXES; MYOFIBRILLAR MYOPATHIES; INTERMEDIATE-FILAMENTS Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26529