Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review

Journal of Clinical Medicine

KarolinaM. Stepien¹  Federico Roncaroli²  Mark Roberts³  ChristianJ. Hendriksz⁴  Iain Hargreaves⁵  RobertA. Heaton⁵  Nadia Turton⁵ 

[1] Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK;Division of Neuroscience and Experimental Psychology, School of Biology, Medicine and Health, University of Manchester and Manchester Centre for Clinical Neuroscience, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK;Neurology Department, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK;Paediatrics and Child Health, Steve Biko Academic Unit, University of Pretoria, 0002 Pretoria, South Africa;School of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UK;

关键词: mitochondrial dysfunction;    lysosomal storage diseases;    oxidative stress;    inflammation;    reactive oxygen species;    autophagy;   

DOI  :  10.3390/jcm9082596

来源: DOAJ

【 摘 要 】

Mitochondrial dysfunction is emerging as an important contributory factor to the pathophysiology of lysosomal storage disorders (LSDs). The cause of mitochondrial dysfunction in LSDs appears to be multifactorial, although impaired mitophagy and oxidative stress appear to be common inhibitory mechanisms shared amongst these heterogeneous disorders. Once impaired, dysfunctional mitochondria may impact upon the function of the lysosome by the generation of reactive oxygen species as well as depriving the lysosome of ATP which is required by the V-ATPase proton pump to maintain the acidity of the lumen. Given the reported evidence of mitochondrial dysfunction in LSDs together with the important symbiotic relationship between these two organelles, therapeutic strategies targeting both lysosome and mitochondrial dysfunction may be an important consideration in the treatment of LSDs. In this review we examine the putative mechanisms that may be responsible for mitochondrial dysfunction in reported LSDs which will be supplemented with morphological and clinical information.

【 授权许可】

Unknown