GATA3 controls mitochondrial biogenesis in primary human CD4+ T cells during DNA damage
Lauren A. Callender, Johannes Schroth, Elizabeth C. Carroll, Lisa E.L. Romano, Eleanor Hendy, Audrey Kelly, Paul Lavender, Arne N. Akbar, J. Paul Chapple, Sian M. Henson
Received Date: 14th May 20
GATA binding protein 3 (GATA3) has traditionally been regarded as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper (Th) 2 cells. However, increasing evidence shows that GATA3 is involved in a myriad of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. We show here a previously unknown mechanism utilized by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the binding of GATA3, AMP-activated protein kinase (AMPK), peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α), nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 3 (SOD3) to the DNA damage repair (DDR) component ATR. These findings extend the pleotropic nature of GATA3 and highlight the potential for GATA3-targeted cell manipulation for clinical interventions.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.