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Suppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate.
- Source :
-
Developmental cell [Dev Cell] 2019 Jun 03; Vol. 49 (5), pp. 748-763.e7. Date of Electronic Publication: 2019 May 16. - Publication Year :
- 2019
-
Abstract
- Oxygen (O <subscript>2</subscript> ) is both an indispensable metabolic substrate and a regulatory signal that controls the activity of Hypoxia-Inducible Factor 1α (Hif1a), a mediator of the cellular adaptation to low O <subscript>2</subscript> tension (hypoxia). Hypoxic cells require Hif1a to survive. Additionally, Hif1a is an inhibitor of mitochondrial respiration. Hence, we hypothesized that enhancing mitochondrial respiration is detrimental to the survival of hypoxic cells in vivo. We tested this hypothesis in the fetal growth plate, which is hypoxic. Our findings show that mitochondrial respiration is dispensable for survival of growth plate chondrocytes. Furthermore, its impairment prevents the extreme hypoxia and the massive chondrocyte death observed in growth plates lacking Hif1a. Consequently, augmenting mitochondrial respiration affects the survival of hypoxic chondrocytes by, at least in part, increasing intracellular hypoxia. We thus propose that partial suppression of mitochondrial respiration is crucial during development to protect the tissues that are physiologically hypoxic from lethal intracellular anoxia.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors physiology
Cell Respiration
Cell Survival
Chondrocytes cytology
DNA-Binding Proteins physiology
Female
High Mobility Group Proteins physiology
Homeodomain Proteins physiology
Hypoxia-Inducible Factor 1, alpha Subunit physiology
Male
Mice
Mice, Inbred C57BL
Chondrocytes physiology
Fetal Development physiology
Growth Plate physiology
Hypoxia physiopathology
Mitochondria physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 49
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 31105007
- Full Text :
- https://doi.org/10.1016/j.devcel.2019.04.029