PDF(Pubmed)
Abstract：
PINK1, mutated in familial forms of Parkinson\'s disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo, we used mito-QC mice in which loss of PINK1 was combined with the mitochondrial-associated POLGD257A mutation. We focused on skeletal muscle as gene expression data indicates that this tissue has the highest PINK1 levels. We found that loss of PINK1 in oxidative hindlimb muscle significantly reduced mitophagy. Of interest, the presence of the POLGD257A mutation, while having a minor effect in most tissues, restored levels of muscle mitophagy caused by the loss of PINK1. Although our observations highlight that multiple mitophagy pathways operate within a single tissue, we identify skeletal muscle as a tissue of choice for the study of PINK1-dependant mitophagy under basal conditions.
摘要：
PINK1，在帕金森氏病的家族形式中突变，线粒体去极化后启动线粒体自噬。然而,由于PINK1的丢失不会改变大多数组织的基础线粒体自噬水平,因此很难在小鼠中从生理上监测该途径.为了在体内进一步表征该途径，我们使用了mito-QC小鼠,其中PINK1缺失与线粒体相关的POLGD257A突变相结合.我们关注骨骼肌，因为基因表达数据表明该组织具有最高的PINK1水平。我们发现氧化性后肢肌肉中PINK1的丢失显着降低了线粒体自噬。感兴趣的，POLGD257A突变的存在，虽然对大多数组织影响较小，PINK1丢失引起的肌肉有丝分裂水平的恢复。尽管我们的观察强调了多个线粒体自噬途径在单个组织中运作，我们确定骨骼肌是基础条件下PINK1依赖性线粒体自噬研究的首选组织.
