Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population.
Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population.
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衰老引起的线粒体功能障碍：两种不同的线粒体群体与组合群体。
DOI：
10.1152/ajpheart.00363.2023
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Lesnefsky,EdwardJ
中科院分区：
文献类型：
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作者：
Chen,Qun;Thompson,Jeremy;Hu,Ying;Lesnefsky,EdwardJ
老年心脏的线粒体功能受损，分离线粒体的研究通常用于评估其功能。心肌线粒体的两个群体，肌膜下线粒体（SSM）和原纤维间线粒体（IFM），受到衰老的影响。然而，这些线粒体的产量，特别是SSM，在小鼠心脏中是有限的，因为心脏尺寸较小。为了解决这个问题，作者开发了一种方法，从单个小鼠心脏中分离SSM和IFM线粒体的混合群体（MIX）。本研究的目的是比较SSM、IFM和来自年轻和老年小鼠心脏的MIX群体之间的线粒体功能。与SSM或IFM的个体产量相比，MIX群体的年轻和老年心脏的总蛋白和柠檬酸合酶活性产量更高。当使用复合物I或IV底物时，与年轻的SSM和IFM相比，老年SSM和IFM中的氧化磷酸化（OXPHOS）减少，以及与年轻心脏相比，从老年心脏分离的MIX群体中的氧化磷酸化（OXPHOS）减少。此外，老化几乎没有影响的敏感性线粒体通透性转换孔（MPTP）在SSM开放，而敏感性增加IFM分离老年心脏和MIX人口从老年心脏相比，相应的人口从年轻的心脏。这些结果表明，线粒体功能障碍存在于老年心脏和线粒体的MIX人口从小鼠心脏的分离是一个潜在的方法来研究线粒体功能在小鼠heart.NEW &值得注意的是，我们开发了两种方法来分离线粒体从一个单一的小鼠心脏。我们使用不同方法分离的线粒体比较了年轻和老年小鼠的线粒体功能。这两种方法都可以成功地用于从单个小鼠心脏中分离心肌线粒体。我们的研究结果提供了灵活性，可以根据研究目的从单个小鼠心脏中分离线粒体。https://ajpheart.podbean.com/e/mitochondrial-isolation-in-aged-hearts/
Mitochondrial function in aged hearts is impaired, and studies of isolated mitochondria are commonly used to assess their function. The two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), are affected by aging. However, the yield of these mitochondria, particularly SSM, is limited in the mouse heart because of the smaller heart size. To address this issue, the authors developed a method to isolate a mixed population (MIX) of SSM and IFM mitochondria from a single mouse heart. The aim of the study was to compare the mitochondrial function between SSM, IFM, and the MIX population from young and aged mouse hearts. The MIX population had a higher yield of total protein and citrate synthase activity from both young and aged hearts compared with the individual yields of SSM or IFM. Oxidative phosphorylation (OXPHOS) decreased in aged SSM and IFM compared with young SSM and IFM, as well as in the MIX population isolated from aged hearts compared with young hearts, when using complex I or IV substrates. Furthermore, aging barely affected the sensitivity to mitochondrial permeability transition pore (MPTP) opening in SSM, whereas the sensitivity was increased in IFM isolated from aged hearts and in the MIX population from aged hearts compared with the corresponding populations isolated from young hearts. These results suggest that mitochondrial dysfunction exists in aged hearts and the isolation of a MIX population of mitochondria from the mouse heart is a potential approach to studying mitochondrial function in the mouse heart.NEW & NOTEWORTHYWe developed two methods to isolate mitochondria from a single mouse heart. We compared mitochondrial function in young and aged mice using mitochondria isolated with different methods. Both methods can be successfully used to isolate cardiac mitochondria from single mouse hearts. Our results provide the flexibility to isolate mitochondria from a single mouse heart based on the purpose of the study.Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/mitochondrial-isolation-in-aged-hearts/.