Jarosz Jan, Ghosh Shouryadipta, Delbridge Lea M D, Petzer Amorita, Hickey Anthony J R, Crampin Edmund J, Hanssen Eric, Rajagopal Vijay
Cell Structure and Mechanobiology Group, Department of Mechanical Engineering, University of Melbourne, Parkville, Australia.
Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Australia.
Am J Physiol Cell Physiol. 2017 Feb 1;312(2):C190-C197. doi: 10.1152/ajpcell.00298.2016. Epub 2016 Nov 30.
Diabetic cardiomyopathy is accompanied by metabolic and ultrastructural alterations, but the impact of the structural changes on metabolism itself is yet to be determined. Morphometric analysis of mitochondrial shape and spatial organization within transverse sections of cardiomyocytes from control and streptozotocin-induced type I diabetic Sprague-Dawley rats revealed that mitochondria are 20% smaller in size while their spatial density increases by 53% in diabetic cells relative to control myocytes. Diabetic cells formed larger clusters of mitochondria (60% more mitochondria per cluster) and the effective surface-to-volume ratio of these clusters increased by 22.5%. Using a biophysical computational model we found that this increase can have a moderate compensatory effect by increasing the availability of ATP in the cytosol when ATP synthesis within the mitochondrial matrix is compromised.
糖尿病性心肌病伴有代谢和超微结构改变,但结构变化对代谢本身的影响尚待确定。对来自对照和链脲佐菌素诱导的I型糖尿病Sprague-Dawley大鼠心肌细胞横切面中线粒体形状和空间组织的形态计量分析显示,与对照心肌细胞相比,糖尿病细胞中的线粒体尺寸小20%,而其空间密度增加53%。糖尿病细胞形成更大的线粒体簇(每簇线粒体多60%),这些簇的有效表面积与体积之比增加22.5%。使用生物物理计算模型,我们发现当线粒体基质内的ATP合成受损时,这种增加可通过提高细胞质中ATP的可用性而产生适度的代偿作用。