Mitochondria integrity is affected by excess cellular glucose influx in the absence of TXNIP

Excess cellular glucose uptake has detrimental effects on cells, yet the mechanism is not fully understood. TXNIP is a negative regulator of glucose uptake by directly facilitating Glut1-4 endocytosis while integrating metabolic and growth factor signals. Using TXNIP KO mouse as a model of excess cellular glucose uptake, we study the effect of glucose on mitochondria integrity in the brown adipose tissue (BAT). We found that the upregulated lipogenesis from excess glucose leads to shorter and more saturated lipid composition in cellular membranes, including mitochondria membrane, which then affects mitochondria integrity under stress. This result also extends to the heart which does not carry out its own lipogenesis. Ketogenic diet can be used to rescue the defect.