Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review
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 mechani...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/8/2596 |
| _version_ | 1797559045737938944 |
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| author | Karolina M. Stepien Federico Roncaroli Nadia Turton Christian J. Hendriksz Mark Roberts Robert A. Heaton Iain Hargreaves |
| author_facet | Karolina M. Stepien Federico Roncaroli Nadia Turton Christian J. Hendriksz Mark Roberts Robert A. Heaton Iain Hargreaves |
| author_sort | Karolina M. Stepien |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:40:10Z |
| format | Article |
| id | doaj.art-c0ad71572dab44ccb9a6096a74d2e4b0 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T17:40:10Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-c0ad71572dab44ccb9a6096a74d2e4b02023-11-20T09:44:46ZengMDPI AGJournal of Clinical Medicine2077-03832020-08-0198259610.3390/jcm9082596Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A ReviewKarolina M. Stepien0Federico Roncaroli1Nadia Turton2Christian J. Hendriksz3Mark Roberts4Robert A. Heaton5Iain Hargreaves6Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, Salford M6 8HD, UKDivision 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, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKPaediatrics and Child Health, Steve Biko Academic Unit, University of Pretoria, 0002 Pretoria, South AfricaNeurology Department, Salford Royal NHS Foundation Trust, Salford M6 8HD, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKSchool of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, UKMitochondrial 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.https://www.mdpi.com/2077-0383/9/8/2596mitochondrial dysfunctionlysosomal storage diseasesoxidative stressinflammationreactive oxygen speciesautophagy |
| spellingShingle | Karolina M. Stepien Federico Roncaroli Nadia Turton Christian J. Hendriksz Mark Roberts Robert A. Heaton Iain Hargreaves Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review Journal of Clinical Medicine mitochondrial dysfunction lysosomal storage diseases oxidative stress inflammation reactive oxygen species autophagy |
| title | Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review |
| title_full | Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review |
| title_fullStr | Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review |
| title_full_unstemmed | Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review |
| title_short | Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review |
| title_sort | mechanisms of mitochondrial dysfunction in lysosomal storage disorders a review |
| topic | mitochondrial dysfunction lysosomal storage diseases oxidative stress inflammation reactive oxygen species autophagy |
| url | https://www.mdpi.com/2077-0383/9/8/2596 |
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