ArticleCell death and differentiation2021
Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Neuropsychological functioning and quality of life in congenital myopathies: a systematic review of children and caregiver outcomes.Frontiers in medicine · 2026Pooled it
- OXPHOS complex deficiency in congenital myopathy: A systematic review.European journal of clinical investigation · 2025Pooled it
- Mitochondria‑associated endoplasmic reticulum membranes in degenerative musculoskeletal disorders: Mechanistic evidence and therapeutic perspectives (Review).Molecular medicine reports · 2026Review
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- ER proteostasis meets mitochondrial function: contact sites as hubs of communication and therapeutic targets.The FEBS journal · 2026Review
- PACS2 Alleviates Sepsis-Induced Myopathy by Activating ERK-MAPK Signalling Pathway to Suppress ER-Phagy.Journal of cachexia, sarcopenia and muscle · 2026Article
- Metabolic adaptation to IMMT deficiency through the ATF6-PPARγ axis is contingent on TP53 mutation status in breast cancer.Cell death & disease · 2026Article
- Selenoprotein N and SEPN1-Related Myopathies: Mechanisms, Models, and Therapeutic Perspectives.Biomolecules · 2026Review
- Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Pyrazolone-based ERO1 inhibitors in ERO1-driven triple-negative breast cancer and SEPN1-related myopathy: Structure-activity relationship and therapeutic potential.Pharmacological research · 2025Article
- Review
- The MFN2 Q367H variant reveals a novel pathomechanism connected to mtDNA-mediated inflammation.Life science alliance · 2025Article
- Zebrafish and cellular models of SELENON-Congenital myopathy exhibit novel embryonic and metabolic phenotypes.Skeletal muscle · 2025Article
- SELENON-related myopathy as a cause of acute respiratory failure in middle age: a case report.Journal of medical case reports · 2025Article
- Creatine transporter (SLC6A8) knockout mice exhibit reduced muscle performance, disrupted mitochondrial CaCell death & disease · 2025Article
- Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.Frontiers in cardiovascular medicine · 2025Review
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA.Cell reports. Medicine · 2024Article
- Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.Journal of neuromuscular diseases · 2024Article
- Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired.
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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.