ArticleCommunications biology2022
Inter-organellar and systemic responses to impaired mitochondrial matrix protein import in skeletal muscle.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Inference of upstream-mutation and metabolomic-signature causality identifies prognostic biomarkers and therapeutic targets in pancreatic cancer.Nature communications · 2026Article
- Tuning the Hsp70 chaperone cycle: emerging roles of GrpE-like nucleotide exchange factors in proteostasis and organelle function.Protein & cell · 2026Review
- c-Myc/GRPEL1 maintains fatty acid synthesis via FASN to support PDAC cell proliferation.Cell death & disease · 2026Article
- Metabolic costs and trade-offs of hypermetabolism in human motor neurons with ATP synthase deficiency.Communications biology · 2025Article
- In vivo mechano-tissue engineering by hydrogels capable of transmitting intercellular mechanical stress.Nature communications · 2025Article
- Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure.Nature communications · 2025Article
- Mitochondrial Maintenance in Skeletal Muscle.Cold Spring Harbor perspectives in biology · 2025Review
- Article
- Identification and Validation of the Potential Key Biomarkers for Atopic Dermatitis Mitochondrion by Learning Algorithms.Journal of inflammation research · 2025Article
- Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70.Nature communications · 2024Article
- Preferential binding of ADP-bound mitochondrial HSP70 to the nucleotide exchange factor GRPEL1 over GRPEL2.Protein science : a publication of the Protein Society · 2024Article
- Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70.bioRxiv : the preprint server for biology · 2024Article
- From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.International journal of molecular sciences · 2023Review
- Mitochondrial Dysfunction as an Underlying Cause of Skeletal Muscle Disorders.International journal of molecular sciences · 2022Review
- Better Together: Interorganellar Communication in the Regulation of Proteostasis.Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Effective protein import from cytosol is critical for mitochondrial functions and metabolic regulation. We describe here the mammalian muscle-specific and systemic consequences to disrupted mitochondrial matrix protein import by targeted deletion of the mitochondrial HSP70 co-chaperone GRPEL1. Muscle-specific loss of GRPEL1 caused rapid muscle atrophy, accompanied by shut down of oxidative phosphorylation and mitochondrial fatty acid oxidation, and excessive triggering of proteotoxic stress responses. Transcriptome analysis identified new responders to mitochondrial protein import toxicity, such as the neurological disease-linked intermembrane space protein CHCHD10. Besides communication with ER and nucleus, we identified crosstalk of distressed mitochondria with peroxisomes, in particular the induction of peroxisomal Acyl-CoA oxidase 2 (ACOX2), which we propose as an ATF4-regulated peroxisomal marker of integrated stress response. Metabolic profiling indicated fatty acid enrichment in muscle, a shift in TCA cycle intermediates in serum and muscle, and dysregulated bile acids. Our results demonstrate the fundamental importance of GRPEL1 and provide a robust model for detecting mammalian inter-organellar and systemic responses to impaired mitochondrial matrix protein import and folding.
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