miR-181a regulates p62/SQSTM1, parkin, and protein DJ-1 promoting mitochondrial dynamics in skeletal muscle aging
| Autor: | Rachel McCormick, Brian McDonagh, Caroline Chinda, Katarzyna Goljanek-Whysall, Ana Soriano-Arroquia |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteomics Protein DJ-1 Ubiquitin-Protein Ligases Population Protein Deglycase DJ-1 Mitochondrion Biology Parkin miR‐181a 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation microRNA Mitophagy Sequestosome-1 Protein medicine Animals parkin skeletal muscle education Muscle Skeletal Cells Cultured Cellular Senescence 030304 developmental biology 0303 health sciences education.field_of_study aging p62 Skeletal muscle Cell Biology Original Articles Muscle atrophy Cell biology Mitochondria Mice Inbred C57BL protein DJ‐1 MicroRNAs 030104 developmental biology medicine.anatomical_structure mitophagy Ageing Original Article medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell AGING CELL |
| ISSN: | 1474-9726 |
| Popis: | 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. We identified a global regulator of mitochondrial dynamics during skeletal muscle aging, miR‐181a. Downregulation of miR‐181a with age in skeletal muscle was associated with disrupted mitochondrial dynamics. miR‐181a targets regulators of autophagic machinery in C2C12 and promotes mitochondrial turnover. Restoration of miR‐181a in old muscle restores myofiber size and force. |
| Databáze: | OpenAIRE |
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