线粒体在心脏功能中的多方面作用:见解和方法。

IF 8.2 2区 生物学 Q1 CELL BIOLOGY
Sriram Ravindran, Christoph D Rau
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引用次数: 0

摘要

即使到了 21 世纪,心血管疾病(CVD)仍然是全球的经济负担,85% 的死亡是由心脏病发作造成的。尽管在减少风险因素和加强药物治疗策略方面做出了努力,但在疾病进展的早期识别和受损心脏的功能恢复方面仍然存在挑战。线粒体功能障碍是心血管疾病发病机制中的一个关键因素,由于它在其他并存疾病中的作用,针对线粒体功能障碍的研究一直不太成功。此外,线粒体是唯一一个具有agathokakological功能的细胞器,对细胞来说既是良药也是毒药。在这篇综述中,我们描述了心脏线粒体的起源,以及异质体和线粒体亚群(即纤维间、小球下、核周和核内线粒体)在维持心脏功能和疾病相关重塑中的作用。我们讨论了线粒体与细胞核逆行通讯的累积证据,强调有必要使用全基因组关联研究(GWAS)等方法研究特定细胞器功能与心血管疾病的基因型与表型关系。最后,我们讨论了计算方法与单细胞测序技术相结合的实用性,以应对基因筛选在鉴定异质性和心血管疾病相关基因方面的挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The multifaceted role of mitochondria in cardiac function: insights and approaches.

Cardiovascular disease (CVD) remains a global economic burden even in the 21st century with 85% of deaths resulting from heart attacks. Despite efforts in reducing the risk factors, and enhancing pharmacotherapeutic strategies, challenges persist in early identification of disease progression and functional recovery of damaged hearts. Targeting mitochondrial dysfunction, a key player in the pathogenesis of CVD has been less successful due to its role in other coexisting diseases. Additionally, it is the only organelle with an agathokakological function that is a remedy and a poison for the cell. In this review, we describe the origins of cardiac mitochondria and the role of heteroplasmy and mitochondrial subpopulations namely the interfibrillar, subsarcolemmal, perinuclear, and intranuclear mitochondria in maintaining cardiac function and in disease-associated remodeling. The cumulative evidence of mitochondrial retrograde communication with the nucleus is addressed, highlighting the need to study the genotype-phenotype relationships of specific organelle functions with CVD by using approaches like genome-wide association study (GWAS). Finally, we discuss the practicality of computational methods combined with single-cell sequencing technologies to address the challenges of genetic screening in the identification of heteroplasmy and contributory genes towards CVD.

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来源期刊
CiteScore
11.00
自引率
0.00%
发文量
180
期刊介绍: Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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