Universität zu Köln

Bubb, Kristina ORCID: 0000-0002-8457-0566, Holzer, Tatjana, Nolte, Janica L., Krueger, Marcus, Wilson, Richard, Schloetzer-Schrehardt, Ursula, Brinckmann, Juergen, Altmueller, Janine, Aszodi, Attila, Fleischhauer, Lutz, Clausen-Schaumann, Hauke ORCID: 0000-0002-9413-0310, Probst, Kristina and Brachvogel, Bent (2021). Mitochondrial respiratory chain function promotes extracellular matrix integrity in cartilage. J. Biol. Chem., 297 (4). AMSTERDAM: ELSEVIER. ISSN 1083-351X

Full text not available from this repository.

Abstract

Energy metabolism and extracellular matrix (ECM) function together orchestrate and maintain tissue organization, but crosstalk between these processes is poorly understood. Here, we used single-cell RNA-Seq (scRNA-Seq) analysis to uncover the importance of the mitochondrial respiratory chain for ECM homeostasis in mature cartilage. This tissue produces large amounts of a specialized ECM to promote skeletal growth during development and maintain mobility throughout life. A combined approach of high-resolution scRNA-Seq, mass spectrometry/matrisome analysis, and atomic force microscopy was applied to mutant mice with cartilage-specific inactivation of respiratory chain function. This genetic inhibition in cartilage results in the expansion of a central area of 1-month-old mouse femur head cartilage, showing disorganized chondrocytes and increased deposition of ECM material. scRNASeq analysis identified a cell cluster-specific decrease in mitochondrial DNA-encoded respiratory chain genes and a unique regulation of ECM-related genes in nonarticular chondrocytes. These changes were associated with alterations in ECM composition, a shift in collagen/noncollagen protein content, and an increase of collagen crosslinking and ECM stiffness. These results demonstrate that mitochondrial respiratory chain dysfunction is a key factor that can promote ECM integrity and mechanostability in cartilage and presumably also in many other tissues.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bubb, Kristina UNSPECIFIED orcid.org/0000-0002-8457-0566 UNSPECIFIED Holzer, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Janica L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilson, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloetzer-Schrehardt, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Aszodi, Attila UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleischhauer, Lutz UNSPECIFIED UNSPECIFIED UNSPECIFIED Clausen-Schaumann, Hauke UNSPECIFIED orcid.org/0000-0002-9413-0310 UNSPECIFIED Probst, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-596550
DOI:	10.1016/j.jbc.2021.101224
Journal or Publication Title:	J. Biol. Chem.
Volume:	297
Number:	4
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLLAGEN; EXPRESSION; PROTEIN; OSSIFICATION; CHONDROCYTES; DEFICIENCY; ACTIVATION; MATRILIN-1; IMBALANCE; MMP-10 Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59655