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© Serge Bonnefoy et Monica Diez Silva
Révélation par immunofluorescence de la présence de la protéine Pf155/RESA dans les globules rouges infectés par Plasmodium falciparum.
Publication : Developmental cell

Redox regulation by Pitx2 and Pitx3 is critical for fetal myogenesis

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Developmental cell - 27 May 2014

L'honoré A, Commère PH, Ouimette JF, Montarras D, Drouin J, Buckingham M

Link to Pubmed [PMID] – 24871946

Dev. Cell 2014 May;29(4):392-405

During development, major metabolic changes occur as cells become more specialized within a lineage. In the case of skeletal muscle, differentiation is accompanied by a switch from a glycolytic proliferative progenitor state to an oxidative postmitotic differentiated state. Such changes require extensive mitochondrial biogenesis leading to increased reactive oxygen species (ROS) production that needs to be balanced by an antioxidant system. Our analysis of double conditional Pitx2/3 mouse mutants, both in vivo during fetal myogenesis and ex vivo in primary muscle cell cultures, reveals excessive upregulation of ROS levels leading to DNA damage and apoptosis of differentiating cells. This is a consequence of downregulation of Nrf1 and genes for antioxidant enzymes, direct targets of Pitx2/3, leading to decreased expression of antioxidant enzymes, as well as impairment of mitochondrial function. Our analysis identifies Pitx2 and Pitx3 as key regulators of the intracellular redox state preventing DNA damage as cells undergo differentiation.

http://www.ncbi.nlm.nih.gov/pubmed/24871946