Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Lee Medical Building, 414 E Clark Street, Vermillion, SD 57069, USA.
Cardiovasc Res. 2010 Jan 15;85(2):253-62. doi: 10.1093/cvr/cvp287. Epub 2009 Aug 20.
Protein quality control (PQC) depends on elegant collaboration between molecular chaperones and targeted proteolysis in the cell. The latter is primarily carried out by the ubiquitin-proteasome system, but recent advances in this area of research suggest a supplementary role for the autophagy-lysosomal pathway in PQC-related proteolysis. The (patho)physiological significance of PQC in the heart is best illustrated in cardiac proteinopathy, which belongs to a family of cardiac diseases caused by expression of aggregation-prone proteins in cardiomyocytes. Cardiac proteasome functional insufficiency (PFI) is best studied in desmin-related cardiomyopathy, a bona fide cardiac proteinopathy. Emerging evidence suggests that many common forms of cardiomyopathy may belong to proteinopathy. This review focuses on examining current evidence, as it relates to the hypothesis that PFI impairs PQC in cardiomyocytes and contributes to the progression of cardiac proteinopathies to heart failure.
蛋白质质量控制（PQC）依赖于细胞内分子伴侣和靶向蛋白水解之间的精巧协作。后者主要由泛素-蛋白酶体系统完成，但该研究领域的最新进展表明，自噬溶酶体途径在 PQC 相关蛋白水解中发挥补充作用。PQC 在心脏中的（病理）生理学意义在心脏蛋白病变中得到了最好的说明，心脏蛋白病变属于一类由心肌细胞中易于聚集的蛋白质表达引起的心脏疾病。心肌蛋白酶体功能不全（PFI）在结蛋白相关性心肌病中得到了最好的研究，这是一种真正的心脏蛋白病变。新出现的证据表明，许多常见形式的心肌病可能属于蛋白病变。这篇综述重点探讨了目前的证据，这些证据与 PFI 损害心肌细胞中 PQC 并导致心脏蛋白病变进展为心力衰竭的假说有关。
