Navratil Marian, Terman Alexei, Arriaga Edgar A
Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN, USA.
Exp Cell Res. 2008 Jan 1;314(1):164-72. doi: 10.1016/j.yexcr.2007.09.013. Epub 2007 Sep 25.
Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giant mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells.
由于自噬不足，巨大线粒体在衰老或患病的有丝分裂后细胞中积累，而自噬通常负责线粒体的降解。我们报告称，在培养的大鼠成肌细胞中，由于自噬受到抑制而积累的巨大线粒体具有低内膜电位，并且彼此之间以及与正常线粒体均不融合。除了巨大线粒体中的线粒体内膜电位较低外，这些线粒体中OPA1线粒体融合蛋白的数量也较低，但线粒体融合蛋白2（Mfn2）的丰度保持不变。这些因素的组合可能解释了巨大线粒体中缺乏线粒体融合的现象，并暗示功能失调的巨大线粒体无法通过与功能正常的线粒体融合并交换其内容物来恢复其功能。这些发现对于理解有丝分裂后细胞中与年龄相关的线粒体损伤积累机制具有重要意义。
