Rosca Mariana G, Hoppel Charles L
Center for Mitochondrial Diseases and Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
J Bioenerg Biomembr. 2009 Apr;41(2):107-12. doi: 10.1007/s10863-009-9215-9.
This minireview focuses on the impairment of function in cardiac mitochondria in heart failure (HF). It is generally accepted that chronic energy starvation leads to cardiac mechanical dysfunction in HF. Mitochondria are the primary ATP generator for the heart. Current evidence suggests that the assembly of the electron transport chain (ETC) into respirasomes provides structural support for mitochondrial oxidative phosphorylation by facilitating electron channeling and perhaps by preventing electron leak and superoxide production. Defects have been purported to occur in the individual ETC complexes or components of the phosphorylation apparatus in HF, but these defects have not been linked to impaired mitochondrial function. Moreover, studies that reported decreased mitochondrial oxidative phosphorylation in HF did not identify the site of the defect. We propose a sequential mechanistic pathway in which the decrease in functional respirasomes in HF is the primary event causing decreased oxidative phosphorylation and increased reactive oxygen species production, leading to a progressive decrease in cardiac performance.
本综述聚焦于心力衰竭（HF）时心脏线粒体功能的损害。人们普遍认为，慢性能量饥饿会导致HF时心脏机械功能障碍。线粒体是心脏产生三磷酸腺苷（ATP）的主要场所。目前的证据表明，电子传递链（ETC）组装成呼吸体通过促进电子传递，或许还通过防止电子泄漏和超氧产生，为线粒体氧化磷酸化提供结构支持。据称HF时个别ETC复合物或磷酸化装置的组分存在缺陷，但这些缺陷与线粒体功能受损并无关联。此外，报道HF时线粒体氧化磷酸化降低的研究并未确定缺陷位点。我们提出了一条连续的机制途径，即HF时功能性呼吸体减少是导致氧化磷酸化降低和活性氧产生增加的主要事件，进而导致心脏功能逐渐下降。
