Unknown

Dataset Information

0

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


ABSTRACT: 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. While fatty acid uptake was increased, fatty acid oxidation was impaired in T2D CD8+ EMRA T cells, which also showed an accumulation of lipid droplets and decreased AMPK activity. Increasing glucose and fatty acids in healthy CD8+ T cells resulted in increased p-p53 expression and a fragmented mitochondrial morphology, similar to that observed in T2D CD8+ EMRA T cells. The resulting mitochondrial changes are likely to have a profound effect on T cell function. Consequently, a better understanding of these metabolic abnormalities is crucial as metabolic manipulation of these cells may restore correct T cell function and help reduce the impact of T cell dysfunction in T2D.

SUBMITTER: Callender L 

PROVIDER: S-EPMC9261431 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3149100 | biostudies-literature
| S-EPMC2754898 | biostudies-other
| S-EPMC3412383 | biostudies-literature
| S-EPMC7486921 | biostudies-literature
| S-EPMC6237609 | biostudies-literature
| S-EPMC3682281 | biostudies-other
| S-EPMC556259 | biostudies-literature
2022-10-18 | PXD033714 | Pride
| S-EPMC2947400 | biostudies-literature
| S-EPMC3422477 | biostudies-literature