Academic Journal
Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases
| العنوان: | Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases |
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| المؤلفون: | Holzer, Tatjana, Probst, Kristina, Etich, Julia, Auler, Markus, Georgieva, Veronika S., Bluhm, Björn, Frie, Christian, Heilig, Juliane, Niehoff, Anja, Nüchel, Julian, Plomann, Markus, Seeger, Jens M., Kashkar, Hamid, Baris, Olivier R., Wiesner, Rudolf J., Brachvogel, Bent |
| المساهمون: | Deutsche Forschungsgemeinschaft |
| المصدر: | Journal of Cell Biology ; volume 218, issue 6, page 1853-1870 ; ISSN 0021-9525 1540-8140 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2019 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1083/jcb.201809056 |
| الاتاحة: | http://dx.doi.org/10.1083/jcb.201809056 https://rupress.org/jcb/article-pdf/218/6/1853/1608500/jcb_201809056.pdf |
| Rights: | http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.BD7841A6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1083/jcb.201809056 |
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