Publikationen: Beitrag in Fachzeitschrift › Zeitschriftenaufsätze › Forschung › Begutachtung
Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. / Holzer, Tatjana; Probst, Kristina; Etich, Julia et al.
in: The Journal of cell biology, Jahrgang 218, Nr. 6, 1853, 03.06.2019, S. 1853-1870.Publikationen: Beitrag in Fachzeitschrift › Zeitschriftenaufsätze › Forschung › Begutachtung
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TY - JOUR
T1 - Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases
AU - Holzer, Tatjana
AU - Probst, Kristina
AU - Etich, Julia
AU - Auler, Markus
AU - Georgieva, Veronika S
AU - Bluhm, Björn
AU - Frie, Christian
AU - Heilig, Juliane
AU - Niehoff, Anja
AU - Nüchel, Julian
AU - Plomann, Markus
AU - Seeger, Jens M
AU - Kashkar, Hamid
AU - Baris, Olivier R
AU - Wiesner, Rudolf J
AU - Brachvogel, Bent
PY - 2019/6/3
Y1 - 2019/6/3
N2 - In childhood, skeletal growth is driven by transient expansion of cartilage in the growth plate. The common belief is that energy production in this hypoxic tissue mainly relies on anaerobic glycolysis and not on mitochondrial respiratory chain (RC) activity. However, children with mitochondrial diseases causing RC dysfunction often present with short stature, which indicates that RC activity may be essential for cartilage-mediated skeletal growth. To elucidate the role of the mitochondrial RC in cartilage growth and pathology, we generated mice with impaired RC function in cartilage. These mice develop normally until birth, but their later growth is retarded. A detailed molecular analysis revealed that metabolic signaling and extracellular matrix formation is disturbed and induces cell death at the cartilage-bone junction to cause a chondrodysplasia-like phenotype. Hence, the results demonstrate the overall importance of the metabolic switch from fetal glycolysis to postnatal RC activation in growth plate cartilage and explain why RC dysfunction can cause short stature in children with mitochondrial diseases.
AB - In childhood, skeletal growth is driven by transient expansion of cartilage in the growth plate. The common belief is that energy production in this hypoxic tissue mainly relies on anaerobic glycolysis and not on mitochondrial respiratory chain (RC) activity. However, children with mitochondrial diseases causing RC dysfunction often present with short stature, which indicates that RC activity may be essential for cartilage-mediated skeletal growth. To elucidate the role of the mitochondrial RC in cartilage growth and pathology, we generated mice with impaired RC function in cartilage. These mice develop normally until birth, but their later growth is retarded. A detailed molecular analysis revealed that metabolic signaling and extracellular matrix formation is disturbed and induces cell death at the cartilage-bone junction to cause a chondrodysplasia-like phenotype. Hence, the results demonstrate the overall importance of the metabolic switch from fetal glycolysis to postnatal RC activation in growth plate cartilage and explain why RC dysfunction can cause short stature in children with mitochondrial diseases.
KW - Animals
KW - Cartilage/metabolism
KW - Cell Differentiation
KW - Chondrocytes/metabolism
KW - Collagen Type II/physiology
KW - DNA Helicases/physiology
KW - Electron Transport
KW - Electron Transport Chain Complex Proteins/antagonists & inhibitors
KW - Energy Metabolism
KW - Growth Disorders/complications
KW - Growth Plate/metabolism
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mitochondrial Diseases/etiology
KW - Mitochondrial Proteins/physiology
KW - Signal Transduction
UR - https://www.mendeley.com/catalogue/b650e083-45fe-3203-9991-667e77525f0c/
U2 - 10.1083/jcb.201809056
DO - 10.1083/jcb.201809056
M3 - Journal articles
C2 - 31085560
VL - 218
SP - 1853
EP - 1870
JO - The Journal of cell biology
JF - The Journal of cell biology
SN - 0021-9525
IS - 6
M1 - 1853
ER -
ID: 4016891