ArticleFree radical biology & medicine2016
Down-regulation of the mitochondrial matrix peptidase ClpP in muscle cells causes mitochondrial dysfunction and decreases cell proliferation.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- Pharmacological inhibition of CLPP stabilizes LETMD1 to boost thermogenesis and alleviate obesity.Adipocyte · 2026Article
- Resistance-CONKAT-seq Guided Discovery of a ClpP Active Natural Product from a Soil Metagenome.ACS chemical biology · 2026Article
- Mode of action guided metagenomic natural product discovery reveals convergent evolution of a ClpP-targeting motif.Nature communications · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- CD36 regulates myogenic differentiation via chronic integrated stress response - implications for muscle aging.Journal of muscle research and cell motility · 2026Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer's disease.Inflammopharmacology · 2025Review
- Mitochondrial Maintenance in Skeletal Muscle.Cold Spring Harbor perspectives in biology · 2025Review
- Discovery of CLPP-1071 as an Exceptionally Potent and Orally Efficacious Human ClpP Activator with Strong In Vivo Antitumor Activity.Journal of medicinal chemistry · 2024Article
- The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.Cancer research · 2024Article
- Mitochondrial stress response and myogenic differentiation.Frontiers in cell and developmental biology · 2024Review
- Intraneuronal β-amyloid impaired mitochondrial proteostasis through the impact on LONP1.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ssu72 phosphatase is essential for thermogenic adaptation by regulating cytosolic translation.Nature communications · 2023Article
- Knowledge mapping of research on the mitochondrial unfolded protein response: a bibliometric and visual analysis.Annals of translational medicine · 2023Article
- ONC201 Suppresses Neuroblastoma Growth by Interrupting Mitochondrial Function and Reactivating Nuclear ATRX Expression While Decreasing MYCN.International journal of molecular sciences · 2023Article
- From mitochondria to sarcopenia: role of 17β-estradiol and testosterone.Frontiers in endocrinology · 2023Review
- Inhibition of High-Temperature Requirement Protein A2 Protease Activity Represses Myogenic Differentiation via UPRmt.International journal of molecular sciences · 2022Article
- Mitochondria: intracellular sentinels of infections.Medical microbiology and immunology · 2022Review
- HRAS germline mutations impair LKB1/AMPK signaling and mitochondrial homeostasis in Costello syndrome models.The Journal of clinical investigation · 2022Article
- Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response.International journal of molecular sciences · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The caseinolytic peptidase P (ClpP) is the endopeptidase component of the mitochondrial matrix ATP-dependent ClpXP protease. ClpP degrades unfolded proteins to maintain mitochondrial protein homeostasis and is involved in the initiation of the mitochondrial unfolded protein response (UPR(mt)). Outside of an integral role in the UPR(mt), the cellular function of ClpP is not well characterized in mammalian cells. To investigate the role of ClpP in mitochondrial function, we generated C2C12 muscle cells that are deficient in ClpP using siRNA or stable knockdown using lentiviral transduction. Reduction of ClpP levels by ~70% in C2C12 muscle cells resulted in a number of mitochondrial alterations including reduced mitochondrial respiration and reduced oxygen consumption rate in response to electron transport chain (ETC) complex I and II substrates. The reduction in ClpP altered mitochondrial morphology, changed the expression level of mitochondrial fission protein Drp1 and blunted UPR(mt) induction. In addition, ClpP deficient cells showed increased generation of reactive oxygen species (ROS) and decreased membrane potential. At the cellular level, reduction of ClpP impaired myoblast differentiation, cell proliferation and elevated phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) suggesting an inhibition of translation. Our study is the first to define the effects of ClpP deficiency on mitochondrial function in muscle cells in vitro. In addition, we have uncovered novel effects of ClpP on mitochondrial morphology, cell proliferation and protein translation pathways in muscle cells.
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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.