Belosludtseva Natalia V, Serov Dmitriy A, Starinets Vlada S, Penkov Nikita V, Belosludtsev Konstantin N
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilov St. 38, 119991 Moscow, Russia.
Int J Mol Sci. 2023 Aug 6;24(15):12485. doi: 10.3390/ijms241512485.
The effect of hyperglycemia on the morphology of individual mitochondria and the state of the mitochondrial network in primary mouse lung microvascular endotheliocytes and human dermal fibroblasts has been investigated. The cells were exposed to high (30 mM) and low (5.5 mM) glucose concentrations for 36 h. In primary endotheliocytes, hyperglycemic stress induced a significant increase in the number of mitochondria and a decrease in the interconnectivity value of the mitochondrial network, which was associated with a decrease in the mean size of the mitochondria. Analysis of the mRNA level of the genes of proteins responsible for mitochondrial biogenesis and mitophagy revealed an increase in the expression level of the , , and genes, indicating stimulated mitochondrial turnover in endotheliocytes under high glucose conditions. In primary fibroblasts, hyperglycemia caused a decrease in the number of mitochondria and an increase in their size. As a result, the mitochondria exhibited higher values for elongation. In parallel, the mRNA level of the and genes in fibroblasts exposed to hyperglycemia was reduced. These findings indicate that high glucose concentrations induced cell-specific morphological rearrangements of individual mitochondria and the mitochondrial network, which may be relevant during mitochondria-targeted drug testing and therapy for hyperglycemic and diabetic conditions.
研究了高血糖对原代小鼠肺微血管内皮细胞和人皮肤成纤维细胞中单个线粒体形态及线粒体网络状态的影响。将细胞暴露于高（30 mM）和低（5.5 mM）葡萄糖浓度下36小时。在原代内皮细胞中，高血糖应激导致线粒体数量显著增加，线粒体网络的互连值降低，这与线粒体平均大小的减小有关。对负责线粒体生物发生和线粒体自噬的蛋白质基因的mRNA水平分析显示， 、 和 基因的表达水平增加，表明在高糖条件下内皮细胞中的线粒体更新受到刺激。在原代成纤维细胞中，高血糖导致线粒体数量减少，大小增加。结果，线粒体表现出更高的伸长值。同时，暴露于高血糖的成纤维细胞中 和 基因的mRNA水平降低。这些发现表明，高糖浓度诱导了单个线粒体和线粒体网络的细胞特异性形态重排，这在针对线粒体的药物测试以及高血糖和糖尿病状况的治疗中可能具有相关性。
