Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases

Abstract : 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.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [78 références]  Voir  Masquer  Télécharger

https://hal.univ-angers.fr/hal-02348135
Contributeur : Olivier Baris <>
Soumis le : mardi 5 novembre 2019 - 12:35:03
Dernière modification le : jeudi 7 novembre 2019 - 13:06:44

Fichier

49858_2_merged_1555081793.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Tatjana Holzer, Kristina Probst, Julia Etich, Markus Auler, Veronika Georgieva, et al.. Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. Journal of Cell Biology, Rockefeller University Press, 2019, 218 (6), pp.1853-1870. ⟨10.1083/jcb.201809056⟩. ⟨hal-02348135⟩

Partager

Métriques

Consultations de la notice

15

Téléchargements de fichiers

12