Transit and integration of extracellular mitochondria in human heart cells.
Transit and integration of extracellular mitochondria in human heart cells.
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DOI：
10.1038/s41598-017-17813-0
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发表时间：
2017-12-12
影响因子：
4.6
通讯作者：
McCully JD
中科院分区：
文献类型：
--
作者：
Cowan DB;Yao R;Thedsanamoorthy JK;Zurakowski D;Del Nido PJ;McCully JD
组织缺血对线粒体的功能产生不利影响，导致氧化磷酸化受损，损害了受影响器官的恢复。缺血对线粒体功能的影响已经在心脏中得到了广泛的研究，因为与这一器官的损伤相关的发病率和死亡率。由于传统的保护缺血后心肌细胞活性和收缩功能的方法效果有限，我们开发了一种独特的方法，通过将呼吸活性线粒体移植到损伤区域来保护心脏。我们以前的动物实验表明，将分离的线粒体移植到缺血的心脏组织可以减少细胞死亡，增加能量产生，并改善收缩功能。我们还发现，外源性线粒体注入或灌流到缺血心脏后，很快就会被心肌细胞内化。在这里，我们使用三维超分辨率显微镜和透射电子显微镜来确定内吞外源线粒体在人诱导性多能干细胞来源的心肌细胞和原代心脏成纤维细胞中的命运。我们发现，分离的线粒体在几分钟内被整合到心肌细胞中，然后运输到内小体和溶酶体。大多数外源线粒体从这些隔室逃逸并与内源线粒体网络融合，而其中一些细胞器通过水解而降解。
Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. As conventional methods to preserve cardiac cell viability and contractile function following ischemia are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria to the injured region. Our previous animal experiments showed that transplantation of isolated mitochondria to ischemic heart tissue leads to decreases in cell death, increases in energy production, and improvements in contractile function. We also discovered that exogenously-derived mitochondria injected or perfused into ischemic hearts were rapidly internalised by cardiac cells. Here, we used three-dimensional super-resolution microscopy and transmission electron microscopy to determine the intracellular fate of endocytosed exogenous mitochondria in human iPS-derived cardiomyocytes and primary cardiac fibroblasts. We found isolated mitochondria are incorporated into cardiac cells within minutes and then transported to endosomes and lysosomes. The majority of exogenous mitochondria escape from these compartments and fuse with the endogenous mitochondrial network, while some of these organelles are degraded through hydrolysis.
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内吞作用未插入：多种进入细胞的方法。
影响因子：
44.1
作者：
Kumari S;Mg S;Mayor S
通讯作者：
Mayor S
影响因子：
20.1
作者：
Kornfeld OS;Hwang S;Disatnik MH;Chen CH;Qvit N;Mochly-Rosen D
通讯作者：
Mochly-Rosen D
影响因子：
0.9
作者：
Kitani, T.;Kami, D.;Gojo, S.
通讯作者：
Gojo, S.
DOI：
10.1152/ajpheart.00348.2003
发表时间：
2004-07-01
影响因子：
4.8
作者：
Lesnefsky, EJ;Chen, Q;Hoppel, CL
通讯作者：
Hoppel, CL
影响因子：
6
作者：
Guerra F;Bucci C
通讯作者：
Bucci C