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.

细胞过量摄取葡萄糖会对细胞产生有害影响，但其具体机制尚未完全阐明。TXNIP是葡萄糖摄取的负调控因子，可通过直接促进Glut1-4内吞作用，同时整合代谢与生长因子信号。本研究以TXNIP敲除（TXNIP KO）小鼠作为细胞过量摄取葡萄糖的模型，探究了葡萄糖对棕色脂肪组织（BAT）中线粒体完整性的影响。我们发现，过量葡萄糖诱导的脂肪生成上调会导致包括线粒体膜在内的细胞膜中脂质链更短、饱和程度更高，进而在应激条件下破坏线粒体完整性。该研究结果同样适用于自身无法进行脂肪生成的心脏组织，而生酮饮食可对该缺陷起到挽救作用。