Goljanek-Whysall, Katarzyna 
ORCID: 0000-0001-8166-8800, Soriano-Arroquia, Ana, McCormick, Rachel, Chinda, Caroline and McDonagh, Brian
(2020)
miR-181a regulates p62/SQSTM1, parkin, and protein DJ-1 promoting mitochondrial dynamics in skeletal muscle aging.
AGING CELL, 19 (4).
e13140-.
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miR-181a regulates p62SQSTM1, parkin, and protein DJ-1 promoting mitochondrial dynamics in skeletal muscle aging.pdf - Published version Download (3MB) | Preview |
Abstract
One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during aging concomitant with dysregulation of miR-181a target interactions. Using functional approaches and mito-QC assay, we have established that miR-181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1, and DJ-1 in vitro. Downregulation of miR-181a with age was associated with an accumulation of autophagy-related proteins and abnormal mitochondria. Restoring miR-181a levels in old mice prevented accumulation of p62, DJ-1, and PARK2, and improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA-based interventions for age-related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | aging, miR-181a, mitophagy, p62, parkin, protein DJ-1, skeletal muscle |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Jul 2020 14:03 |
| Last Modified: | 18 Jan 2023 23:46 |
| DOI: | 10.1111/acel.13140 |
| Open Access URL: | https://onlinelibrary.wiley.com/doi/full/10.1111/a... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3093291 |
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