Elsnicova, Barbara, Hornikova, Daniela, Tibenska, Veronika, Kolar, David, Tlapakova, Tereza ORCID: 0000-0001-8841-1573, Schmid, Benjamin ORCID: 0000-0002-9327-2296, Mallek, Markus, Eggers, Britta ORCID: 0000-0002-6553-4631, Schloetzer-Schrehardt, Ursula, Peeva, Viktoriya ORCID: 0000-0001-8007-017X, Berwanger, Carolin, Eberhard, Bettina, Durmus, Hacer, Schultheis, Dorothea, Holtzhausen, Christian, Schork, Karin ORCID: 0000-0003-3756-4347, Marcus, Katrin, Jordan, Jens, Luecke, Thomas ORCID: 0000-0001-6875-6582, van der Ven, Peter F. M., Schroeder, Rolf, Clemen, Christoph S. and Zurmanova, Jitka M. (2022). Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis. Int. J. Mol. Sci., 23 (19). BASEL: MDPI. ISSN 1422-0067

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Abstract

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Elsnicova, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hornikova, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tibenska, VeronikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolar, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tlapakova, TerezaUNSPECIFIEDorcid.org/0000-0001-8841-1573UNSPECIFIED
Schmid, BenjaminUNSPECIFIEDorcid.org/0000-0002-9327-2296UNSPECIFIED
Mallek, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggers, BrittaUNSPECIFIEDorcid.org/0000-0002-6553-4631UNSPECIFIED
Schloetzer-Schrehardt, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peeva, ViktoriyaUNSPECIFIEDorcid.org/0000-0001-8007-017XUNSPECIFIED
Berwanger, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eberhard, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durmus, HacerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultheis, DorotheaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holtzhausen, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schork, KarinUNSPECIFIEDorcid.org/0000-0003-3756-4347UNSPECIFIED
Marcus, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jordan, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luecke, ThomasUNSPECIFIEDorcid.org/0000-0001-6875-6582UNSPECIFIED
van der Ven, Peter F. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clemen, Christoph S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zurmanova, Jitka M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-689256
DOI: 10.3390/ijms231912020
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 23
Number: 19
Date: 2022
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MITOCHONDRIAL CREATINE-KINASE; SKELETAL-MUSCLE; INTERMEDIATE-FILAMENTS; COMPUTATIONAL PLATFORM; ETFDH MUTATIONS; MUTANT DESMIN; FILAMIN C; GENE; CYTOSKELETON; DEFICIENCYMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68925

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