Altered Nutrient Uptake Causes Mitochondrial Dysfunction in Senescent CD8 EMRA T Cells During Type 2 Diabetes.

Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8 EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8 T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8 T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells.

GATA3 induces mitochondrial biogenesis in primary human CD4 T cells during DNA damage.

GATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4 T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4 T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2).