Failed Power Plant Turns Into Mass Murder: New Insight on Mitochondrial Cardiomyopathy.
Failed Power Plant Turns Into Mass Murder: New Insight on Mitochondrial Cardiomyopathy.
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失败的发电厂变成大规模谋杀：对线粒体心肌病的新见解。
DOI：
10.1161/circresaha.117.312288
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发表时间：
2018
影响因子：
20.1
通讯作者：
Tian,Rong
中科院分区：
文献类型：
--
作者：
Lee,ChiFung;Cao,Yang;Tian,Rong
12循环研究2018年1月5日抑制DNA损伤并抑制心肌细胞增殖的出生后窗口，而出生后高氧血症增强DNA损伤和早期细胞周期停滞。12总的来说，DDR的激活似乎是线粒体功能调节细胞周期活性的共同机制。研究中另一个有趣的观察结果是，新生儿心脏中Tfam的缺失不影响心肌细胞的细胞大小，T-小管结构或肌节形态。这些发现表明线粒体对于出生后心肌细胞收缩器的成熟是不可或缺的。然而，目前尚不清楚线粒体功能是否是胚胎发育过程中肌节形成所必需的。Tfam缺陷心肌细胞的收缩机制虽然正常，但其收缩能力受损，钙瞬变减少，提示线粒体功能对成熟心肌细胞的功能至关重要。Zhang等的发现也为线粒体心肌病的新疗法提供了概念基础。然而，在考虑这些发现的转化潜力时，必须考虑模型的几个限制。Tfam缺失是胚胎致死的。类似严重程度的突变不太可能在活产中观察到。作者通过在出生后第0天删除Tfam来测试他们的假设，这在患者中不会发生。然而，ETC（电子传递链）蛋白的其他突变可能在胎儿发育期间避免心肌细胞增殖，但在新生儿阶段产生ROS并触发DDR。这些患者将
12 Circulation Research January 5, 2018 inhibits DNA damage and prolongs the postnatal window of cardiomyocytes proliferation, whereas postnatal hyperoxemia potentiates DNA damage and early cell cycle arrest. 12 Taken together, activation of DDR seems to be a shared mechanism by which mitochondrial function regulates cell cycle activity. Another interesting observation made in the study was that deletion of Tfam in neonatal heart did not affect cell size, T-tubule structure, or sarcomere morphology of cardiomyocytes. These findings suggest that mitochondria are dispensable for the maturation of contractile apparatus in the postnatal cardiomyocyte. It is, however, not clear whether mitochondrial function is required for the formation of sarcomeres during embryonic development. Despite the apparent normal contractile machineries, Tfam-deficient cardiomyocytes showed impaired contractility and reduced calcium transient, suggesting that mitochondrial function is crucial for the function of mature cardiomyocytes.The finding by Zhang et al also provides a conceptual basis for novel therapy of mitochondrial cardiomyopathy. However, several limitations of the model must be taken into account when considering the translational potential of these findings. Tfam deletion is embryonic lethal. Mutations of similar severity are unlikely seen in live birth. The authors tested their hypothesis by deleting Tfam at postnatal day 0, which would not occur in patients. Nevertheless, it is possible that other mutations of ETC (electron transport chain) proteins could spare cardiomyocytes proliferation during fetal development but generate ROS and trigger DDR at neonatal stage. These patients would
影响因子：
11.8
作者：
Hom, Jennifer R.;Quintanilla, Rodrigo A.;Hoffman, David L.;Bentley, Karen L. de Mesy;Molkentin, Jeffery D.;Sheu, Shey-Shing;Porter, George A., Jr.
通讯作者：
Porter, George A., Jr.
影响因子：
10.5
作者：
Lai, Ling;Leone, Teresa C.;Kelly, Daniel P.
通讯作者：
Kelly, Daniel P.