Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada.
Biochim Biophys Acta Mol Basis Dis. 2019 Apr 1;1865(4):782-796. doi: 10.1016/j.bbadis.2018.11.018. Epub 2018 Nov 22.
Recent studies have led to the discovery of multiple mitochondrial quality control (mQC) processes that operate at various scales, ranging from the degradation of proteins by mitochondrial proteases to the degradation of selected cargos or entire organelles in lysosomes. While the mechanisms governing these mQC processes are progressively being delineated, their role and importance remain unclear. Converging evidence however point to a complex system whereby multiple and partly overlapping processes are recruited to orchestrate a cell type specific mQC response that is adapted to the physiological state and level of stress encountered. Knowledge gained from basic model systems of mQC therefore need to be integrated within organ-specific (patho)physiological frameworks. Building on this notion, this article focuses on mQC in the heart, where developmental metabolic reprogramming, sustained contraction, and multiple pathophysiological conditions pose broadly different constraints. We provide an overview of current knowledge of mQC processes, and discuss their implication in cardiac mQC under normal and diseased conditions.
最近的研究发现了多种线粒体质量控制(mQC)过程,这些过程在不同的尺度上运作,从线粒体蛋白酶对蛋白质的降解到溶酶体中对选定货物或整个细胞器的降解。虽然控制这些 mQC 过程的机制正在逐步被描绘出来,但它们的作用和重要性仍然不清楚。然而,越来越多的证据表明,存在一个复杂的系统,其中多个部分重叠的过程被招募来协调特定于细胞类型的 mQC 反应,以适应所遇到的生理状态和应激水平。因此,从 mQC 的基础模型系统中获得的知识需要整合到特定于器官的(病理)生理学框架中。基于这一概念,本文重点介绍了心脏中的 mQC,其中发育代谢重编程、持续收缩和多种病理生理条件带来了广泛不同的限制。我们概述了目前对 mQC 过程的认识,并讨论了它们在正常和患病条件下对心脏 mQC 的影响。