Gaudioso Angel, Garcia-Rozas Patricia, Casarejos Maria Jose, Pastor Oscar, Rodriguez-Navarro Jose Antonio
Cellular Neurobiology Laboratory, Neurobiology Department, UCS-UCM, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Neuropharmacology Laboratory, Neurobiology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
Front Neurosci. 2019 Apr 24;13:329. doi: 10.3389/fnins.2019.00329. eCollection 2019.
Mitochondrial quality control is important in neurological diseases, but in genetic Parkinson's disease caused by mutations in PINK and parkin mitochondrial degradation through autophagy is crucial. Reductions in autophagy and mitophagy are implicated in aging, age related diseases and Parkinson. The parkin null mice (PK-KO) show only a subtle phenotype, apparent with age or with stressors. We have studied the changes in the lipidomic composition of the mitochondrial membranes isolated from the brains of young and old PK-KO mice and compared them to wild type in order to determine possible implications for Parkinson's disease pathology. We observed an increase in the levels of phosphatidylethanolamine in the young PK-KO mice that is lost in the old and correlate to changes in the phosphatidylserine decarboxylase. PK-KO old mice mitochondria showed lower phosphatidylglicerol and phosphatidylinositol levels and higher levels of some forms of hydroxylated ceramides. Regarding cardiolipins there were changes in the degree of saturation mainly with age. The lipidomic composition discriminates between the study groups using partial least square discriminant analysis. We discuss the relevance of the lipid changes for the autophagic activity, the mitophagy, the mitochondrial activity and the Parkinson's disease pathology in absence of parkin.
线粒体质量控制在神经疾病中很重要，但在由PINK和parkin突变引起的遗传性帕金森病中，通过自噬进行线粒体降解至关重要。自噬和线粒体自噬的减少与衰老、年龄相关疾病以及帕金森病有关。parkin基因敲除小鼠（PK-KO）仅表现出轻微的表型，在衰老或受到应激源刺激时才会显现。我们研究了从年轻和年老PK-KO小鼠大脑中分离出的线粒体膜脂质组组成的变化，并将其与野生型进行比较，以确定对帕金森病病理学的可能影响。我们观察到年轻PK-KO小鼠中磷脂酰乙醇胺水平升高，而在年老小鼠中则降低，且这与磷脂酰丝氨酸脱羧酶的变化相关。PK-KO年老小鼠的线粒体显示出较低的磷脂酰甘油和磷脂酰肌醇水平以及某些形式的羟基化神经酰胺水平较高。关于心磷脂，主要随着年龄的增长饱和度程度发生变化。脂质组组成通过偏最小二乘判别分析区分研究组。我们讨论了在缺乏parkin的情况下脂质变化对自噬活性、线粒体自噬、线粒体活性和帕金森病病理学的相关性。
