Bubb K, Holzer T, Nolte JL, Krüger M, Wilson R, Schlötzer-Schrehardt U, Brinckmann J, Altmüller J, Aszodi A, Fleischhauer L, Clausen-Schaumann H, Probst K, Brachvogel B (2021)
Publication Type: Journal article
Publication year: 2021
Book Volume: 279
Article Number: 101224
Journal Issue: 4
DOI: 10.1016/j.jbc.2021.101224
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. scRNA-Seq 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.
APA:
Bubb, K., Holzer, T., Nolte, J.L., Krüger, M., Wilson, R., Schlötzer-Schrehardt, U.,... Brachvogel, B. (2021). Mitochondrial respiratory chain function promotes extracellular matrix integrity in cartilage. Journal of Biological Chemistry, 279(4). https://doi.org/10.1016/j.jbc.2021.101224
MLA:
Bubb, Kristina, et al. "Mitochondrial respiratory chain function promotes extracellular matrix integrity in cartilage." Journal of Biological Chemistry 279.4 (2021).
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