Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis
| Autor: | Jieon Park, Kyusang Yoo, Joonwoo Rhee, Jung-Wee Park, Jong-Seol Kang, Young-Yun Kong, Yong-Chan Ha, Hyerim Park, Inkuk Park, Ye Lynne Kim, Ji-Yun Seo, Young-Woo Jo, Ji Hoon Kim, Sang-Hyeon Hann |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Aging Proteasome Endopeptidase Complex Genotype Science Ubiquitin-Protein Ligases General Physics and Astronomy Skeletal muscle General Biochemistry Genetics and Molecular Biology Article Transcriptome 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Humans Clinical significance Glycolysis Actinin Muscle Skeletal Regulation of gene expression Multidisciplinary Proteasome business.industry HEK 293 cells General Chemistry Muscle atrophy Mice Inbred C57BL Young age Ageing 030104 developmental biology Endocrinology medicine.anatomical_structure HEK293 Cells Gene Expression Regulation medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Age-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1ΔMF) results in alteration of type 2 glycolytic myofibers, muscle atrophy, impaired muscle function, and Actn3 accumulation. After chronic exercise, Mib1ΔMF mice show muscle atrophy even at young age. However, when Actn3 level is downregulated, chronic exercise-induced muscle atrophy is ameliorated. Importantly, the Mib1 and Actn3 levels show clinical relevance in human skeletal muscles accompanied by decrease in skeletal muscle function with age. Together, these findings reveal the significance of the Mib1-Actn3 axis in skeletal muscle maintenance with age and suggest the therapeutic potential for the treatment or amelioration of age-related muscle atrophy. Muscle atrophy is associated with ageing, but the underlying molecular mechanisms are not well understood. Here, they authors show that ablation of the E3 ubiquitin ligase Mib1 is important for myofibre maintenance via a mechanism that involves targeting and degradation of Actn3, and that Mib1 ablation in mice induces muscle atrophy which can be rescued by knockown of Actn3 expression. |
| Databáze: | OpenAIRE |
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