ArticleSkeletal muscle2020
Mitochondrial dysfunction and consequences in calpain-3-deficient muscle.
Article in Skeletal muscle, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- CaMKIIβ Signaling drives expression of metabolic and stress response genes in skeletal muscle, and its loss contributes to the LGMDR1 phenotype.Human molecular genetics · 2026Article
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- French National Protocol for Diagnosis and Care of Calpainopathy (LGMD R1/LGMD D4): consensus guidelines for clinical practice.Orphanet journal of rare diseases · 2026Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Targeting nuclear receptors in muscular dystrophies and regenerative myogenesis.Frontiers in cell and developmental biology · 2026Review
- Recent insights into limb-girdle muscular dystrophy: Impacts, therapy, and challenges.Histology and histopathology · 2025Review
- Calpainopathy (limb-girdle muscular dystrophy type R1): clinical features, diagnostic approaches, and biotechnological treatment methods.Journal of neuromuscular diseases · 2025Review
- Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy.Heliyon · 2024Article
- Mitochondrial Quality Control: A New Perspective in Skeletal Muscle Dysfunction of Chronic Obstructive Pulmonary Disease.Aging and disease · 2024Review
- Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males.Translational exercise biomedicine · 2024Article
- Identification of novel pathogenic variants of Calpain-3 gene in limb girdle muscular dystrophy R1.Orphanet journal of rare diseases · 2024Article
- Identification and functional characterization of a novel heterozygous splice‑site mutation in the calpain 3 gene causes rare autosomal dominant limb‑girdle muscular dystrophy.Experimental and therapeutic medicine · 2024Article
- Annexins and Membrane Repair Dysfunctions in Muscular Dystrophies.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNonsense or loss-of-function mutations in the non-lysosomal cysteine protease calpain-3 result in limb-girdle muscular dystrophy type 2A (LGMD2A). While calpain-3 is implicated in muscle cell differentiation, sarcomere formation, and muscle cytoskeletal remodeling, the physiological basis for LGMD2A has remained elusive.
methodsCell growth, gene expression profiling, and mitochondrial content and function were analyzed using muscle and muscle cell cultures established from healthy and calpain-3-deficient mice. Calpain-3-deficient mice were also treated with PPAR-delta agonist (GW501516) to assess mitochondrial function and membrane repair. The unpaired t test was used to assess the significance of the differences observed between the two groups or treatments. ANOVAs were used to assess significance over time.
resultsWe find that calpain-3 deficiency causes mitochondrial dysfunction in the muscles and myoblasts. Calpain-3-deficient myoblasts showed increased proliferation, and their gene expression profile showed aberrant mitochondrial biogenesis. Myotube gene expression analysis further revealed altered lipid metabolism in calpain-3-deficient muscle. Mitochondrial defects were validated in vitro and in vivo. We used GW501516 to improve mitochondrial biogenesis in vivo in 7-month-old calpain-3-deficient mice. This treatment improved satellite cell activity as indicated by increased MyoD and Pax7 mRNA expression. It also decreased muscle fatigability and reduced serum creatine kinase levels. The decreased mitochondrial function also impaired sarcolemmal repair in the calpain-3-deficient skeletal muscle. Improving mitochondrial activity by acute pyruvate treatment improved sarcolemmal repair.
conclusionOur results provide evidence that calpain-3 deficiency in the skeletal muscle is associated with poor mitochondrial biogenesis and function resulting in poor sarcolemmal repair. Addressing this deficit by drugs that improve mitochondrial activity offers new therapeutic avenues for LGMD2A.
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