Suppressing Mitochondrial Respiration Is Critical for Hypoxia Tolerance in the Fetal Growth Plate

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2019 May 21

PMID 31105007

Citations 36

Authors

Qing Yao

Mohd Parvez Khan

Christophe Merceron

Edward L LaGory

Zachary Tata

Laura Mangiavini

Jiarui Hu

Krishna Vemulapalli

Navdeep S Chandel

Amato J Giaccia

Ernestina Schipani

Affiliations

Soon will be listed here.

Abstract

Oxygen (O) 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 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.

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