Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders

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• 作者：Nicoletta Plotegher¹ ; Michael R. Duchen¹ ; ^{m.duchen@ucl.ac.uk}
• 刊名：Trends in Molecular Medicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：23
• 期：2
• 页码：116-134
• 全文大小：2588 K
• 卷排序：23

文摘

Lysosomal storage disorders (LSDs) are rare inherited debilitating and often fatal disorders. Caused by mutations affecting lysosomal proteins, LSDs are characterized by the accumulation of undegraded material in lysosomes and by lysosomal dysfunction. Although LSDs are multisystemic diseases, the majority display neurologic symptoms and neurodegeneration. Only recently has a role emerged for mitochondrial dysfunction in the pathophysiology of LSDs, suggesting an impact of lysosomal dysfunction on mitochondria. Moreover, mitochondrial damage may also cause lysosomal dysfunction, further supporting the activity of common signaling pathways and crosstalk between the two organelles. In this review we explore the mechanisms linking lysosomal and mitochondrial dysfunction to assess whether specific mitochondrial pathways represent a new therapeutic frontier in the management of LSDs.