Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases.
Animals
Cartilage
/ metabolism
Cell Differentiation
Chondrocytes
/ metabolism
Collagen Type II
/ physiology
DNA Helicases
/ physiology
Electron Transport
Electron Transport Chain Complex Proteins
/ antagonists & inhibitors
Energy Metabolism
Growth Disorders
/ complications
Growth Plate
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondrial Diseases
/ etiology
Mitochondrial Proteins
/ physiology
Signal Transduction
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
03 06 2019
03 06 2019
Historique:
received:
12
09
2018
revised:
12
01
2019
accepted:
12
04
2019
pubmed:
16
5
2019
medline:
10
4
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31085560
pii: jcb.201809056
doi: 10.1083/jcb.201809056
pmc: PMC6548139
doi:
Substances chimiques
Col2a1 protein, mouse
0
Collagen Type II
0
Electron Transport Chain Complex Proteins
0
Mitochondrial Proteins
0
Twnk protein, mouse
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1853-1870Informations de copyright
© 2019 Holzer et al.
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