ArticleJCI insight2022
Frataxin deficiency lowers lean mass and triggers the integrated stress response in skeletal muscle.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Safety and efficacy of individualised exercise and NADThe Lancet. Neurology · 2026Trial
- Neuropathology of Friedreich ataxia and its links to metabolic pathways.Neurodegenerative disease management · 2026Review
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Skeletal Muscle Pathology in Autosomal Recessive Cerebellar Ataxias: Insights from Marinesco-Sjögren Syndrome.International journal of molecular sciences · 2025Review
- Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy.Journal of the American Heart Association · 2025Article
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Insulin Sensitivity and Insulin Secretion in Adults With Friedreich's Ataxia: The Role of Skeletal Muscle.The Journal of clinical endocrinology and metabolism · 2025Observational
- Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study.European journal of neurology · 2025Article
- Dietary and lifestyle interventions for the management of hereditary ataxias.Frontiers in nutrition · 2025Review
- Skeletal Muscle Involvement in Friedreich Ataxia.International journal of molecular sciences · 2024Review
- Interplay of FXN expression and lipolysis in white adipocytes plays a critical role in insulin sensitivity in Friedreich's ataxia mouse model.Scientific reports · 2024Article
- Frataxin Loss Promotes Angiotensin II-Induced Endothelial-to-Mesenchymal Transition.Journal of the American Heart Association · 2024Article
- NAD+ precursors prolong survival and improve cardiac phenotypes in a mouse model of Friedreich's Ataxia.JCI insight · 2024Article
- A peptide derived from TID1S rescues frataxin deficiency and mitochondrial defects in FRDA cellular models.Frontiers in pharmacology · 2024Article
- Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model.iScience · 2023Article
- Continuous, but not intermittent, regimens of hypoxia prevent and reverse ataxia in a murine model of Friedreich's ataxia.Human molecular genetics · 2023Article
- Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich's ataxia.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Friedreich's ataxia (FRDA) is an inherited disorder caused by reduced levels of frataxin (FXN), which is required for iron-sulfur cluster biogenesis. Neurological and cardiac comorbidities are prominent and have been a major focus of study. Skeletal muscle has received less attention despite indications that FXN loss affects it. Here, we show that lean mass is lower, whereas body mass index is unaltered, in separate cohorts of adults and children with FRDA. In adults, lower lean mass correlated with disease severity. To further investigate FXN loss in skeletal muscle, we used a transgenic mouse model of whole-body inducible and progressive FXN depletion. There was little impact of FXN loss when FXN was approximately 20% of control levels. When residual FXN was approximately 5% of control levels, muscle mass was lower along with absolute grip strength. When we examined mechanisms that can affect muscle mass, only global protein translation was lower, accompanied by integrated stress response (ISR) activation. Also in mice, aerobic exercise training, initiated prior to the muscle mass difference, improved running capacity, yet, muscle mass and the ISR remained as in untrained mice. Thus, FXN loss can lead to lower lean mass, with ISR activation, both of which are insensitive to exercise training.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.