Universität zu Köln

Holzer, Tatjana, Probst, Kristina, Etich, Julia ORCID: 0000-0003-3238-6692, Auler, Markus, Georgieva, Veronika S., Bluhm, Bjoern, Frie, Christian, Heilig, Juliane, Niehoff, Anja, Nuechel, Julian, Plomann, Markus, Seeger, Jens M., Kashkar, Hamid, Baris, Olivier R., Wiesner, Rudolf J. and Brachvogel, Bent (2019). Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J. Cell Biol., 218 (6). S. 1853 - 1871. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Holzer, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Probst, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Etich, Julia UNSPECIFIED orcid.org/0000-0003-3238-6692 UNSPECIFIED Auler, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgieva, Veronika S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluhm, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Frie, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilig, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuechel, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Plomann, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Jens M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-146798
DOI:	10.1083/jcb.201809056
Journal or Publication Title:	J. Cell Biol.
Volume:	218
Number:	6
Page Range:	S. 1853 - 1871
Date:	2019
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DIFFERENTIATION FACTOR 15; X COLLAGEN; ELECTRON-TRANSPORT; PLATE CARTILAGE; STRESS-RESPONSE; ER STRESS; MATRIX; EXPRESSION; AUTOPHAGY; CHONDROCYTES Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14679