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生死过程中的线粒体膜脂及其饮食的分子调节:调控熔炉

Mitochondrial membrane lipids in life and death and their molecular modulation by diet: tuning the furnace.

作者信息

Monteiro João P, Morais Catarina M, Oliveira Paulo J, Jurado Amália S

机构信息

CNC - Center for Neuroscience and Cell Biology, UC Biotech Building, University of Coimbra, Lot 8A, Biocant Park, 3060-197 Cantanhede, Portugal.

出版信息

Curr Drug Targets. 2014;15(8):797-810. doi: 10.2174/1389450115666140623115315.

DOI:10.2174/1389450115666140623115315
PMID:24953065
Abstract

The traditional view of mitochondria as cell powerhouses is a matter of common knowledge, but the overall view of these extraordinary organelles has been revolutionized in the last years. In fact, a large number of important and diverse processes take place at the mitochondrial level, which clearly surpass the energy production scope, intruding the critical fragile balance between cell life and death. The entangled biochemistry of mitochondrial membranes has been found to be dependent on specific lipid requirements, with cardiolipin holding a great part of the raised functional interest. Mitochondria contain a complex membrane system, based on a variety of lipids and exquisite asymmetries. Mitochondria lipid membrane composition depends on a tight interplay with the endoplasmic reticulum, from which some of the lipids present in the mitochondrial membranes have to be imported, at least in the form of precursors. Here, we review some external interventions resulting in alterations of mitochondrial lipid content, namely dietary interventions and genetic manipulation. Such manipulations of mitochondrial membrane lipid composition should result in physiological impact, given the importance of lipid-protein interactions within the mitochondrial membrane boundaries. We provide arguments for future experiments using the most modern chemical and biophysical approaches as well as computer simulation studies applied to appropriate biological membrane model systems, in order to identify the effects exerted by diet-induced lipid changes on membrane physical properties.

摘要

线粒体作为细胞动力源的传统观点已是常识,但在过去几年里,人们对这些非凡细胞器的整体认识发生了革命性变化。事实上,线粒体层面发生了大量重要且多样的过程,这些过程明显超出了能量产生的范畴,涉及到细胞生死之间关键的脆弱平衡。已发现线粒体膜复杂的生物化学过程依赖于特定的脂质需求,心磷脂引发了极大的功能研究兴趣。线粒体包含一个基于多种脂质和精细不对称性的复杂膜系统。线粒体脂质膜的组成取决于与内质网的紧密相互作用,线粒体膜中存在的一些脂质至少以前体的形式必须从内质网导入。在此,我们综述了一些导致线粒体脂质含量改变的外部干预措施,即饮食干预和基因操作。鉴于线粒体膜边界内脂质 - 蛋白质相互作用的重要性,这种对线粒体膜脂质组成的操作应该会产生生理影响。我们为未来的实验提供了论据,这些实验将使用最现代的化学和生物物理方法以及应用于合适生物膜模型系统的计算机模拟研究,以确定饮食诱导的脂质变化对膜物理性质的影响。

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