ArticleEMBO molecular medicine2023
LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- CLPP loss confers sex-specific protection from renal ischemia reperfusion injury.Redox biology · 2026Article
- Redox-Mediated Mitochondrial Dysfunction as a Common Pathogenic Axis in Acute Kidney Injury and Chronic Kidney Disease.Biomolecules · 2026Review
- Review
- Reprogramming Mitochondrial Adaptation: LONP1 at the Crossroads of Proteostasis, Metabolism, and Disease.Antioxidants (Basel, Switzerland) · 2026Review
- D-serine and D-alanine supplementation protects against chronic kidney disease.Scientific reports · 2026Article
- Lactylation-mitochondria axis in chronic kidney disease: metabolic reprogramming, epigenetic dysregulation, and therapeutic potential.Molecular and cellular biochemistry · 2026Review
- Exercise attenuates polycystic ovary syndrome development via improved mitochondrial proteostasis.American journal of physiology. Endocrinology and metabolism · 2026Article
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Ketone bodies in kidney diseases: novel insights.Frontiers in immunology · 2026Review
- Effects of enzyme preparations on growth performance, meat quality, and hepatic transcriptome of yaks.Frontiers in veterinary science · 2026Article
- Integrative omics and experimental validation reveal METTL17 and SLC27A1 as biomarkers and potential therapeutic targets in chronic kidney disease.Frontiers in immunology · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Lon peptidase 1 promotes proliferation and metastasis in breast cancer via interleukin 6 signaling.Discover oncology · 2025Article
- Epigenetic Histone β-Hydroxybutyrylation Contributes to Renoprotection by β-Hydroxybutyrate in the Dahl Rat.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Tubular ACSM3 deficiency impairs medium-chain fatty acid metabolism and aggravates kidney fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Low-intensity pulsed ultrasound stimulation to treat renal fibrosis through inhibiting tubular IL-1R.JCI insight · 2025Article
- Suyin Detoxification Prescription Regulates the Klotho and ERK/NF-κB Signaling Pathways to Alleviate Renal Injury.Cell biochemistry and biophysics · 2025Article
- Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells.Journal of translational medicine · 2025Article
- Mitochondrial subtypes in renal ischemia reperfusion injury guide delayed graft function and Long-Term graft prediction.Scientific reports · 2025Article
- Cellular senescence in renal ischemia-reperfusion injury.Chinese medical journal · 2025Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondria comprise the central metabolic hub of cells and their imbalance plays a pathogenic role in chronic kidney disease (CKD). Here, we studied Lon protease 1 (LONP1), a major mitochondrial protease, as its role in CKD pathogenesis is unclear. LONP1 expression was decreased in human patients and mice with CKD, and tubular-specific Lonp1 overexpression mitigated renal injury and mitochondrial dysfunction in two different models of CKD, but these outcomes were aggravated by Lonp1 deletion. These results were confirmed in renal tubular epithelial cells in vitro. Mechanistically, LONP1 downregulation caused mitochondrial accumulation of the LONP1 substrate, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), which disrupted mitochondrial function and further accelerated CKD progression. Finally, computer-aided virtual screening was performed, which identified a novel LONP1 activator. Pharmacologically, the LONP1 activator attenuated renal fibrosis and mitochondrial dysfunction. Collectively, these results imply that LONP1 is a promising therapeutic target for treating CKD.
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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.