ArticleCell2015
Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 125 citations in OpenAlex.
- A mitochondrial insertion directs substrate selection and engagement by the protein unfoldase ClpX.The Journal of biological chemistry · 2026Article
- An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease.Science (New York, N.Y.) · 2026Article
- CLPX acquires an iron-sulfur cluster to sustain mitochondrial proteostasis in cancer cells.Nature communications · 2026Article
- CD73Nature communications · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- A mitochondrial insertion directs substrate selection and engagement by ClpX.bioRxiv : the preprint server for biology · 2026Article
- Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation.Nature communications · 2026Article
- Identification of a NovelGenes · 2025Article
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Mitochondrial proteases and their roles in mitophagy in plants, animals, and yeast.Plant & cell physiology · 2025Review
- The ClpXP protease and the ClpX unfoldase control virulence, cell division, and autolysis inMicrobiology spectrum · 2025Article
- SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.Nature communications · 2025Article
- Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation.bioRxiv : the preprint server for biology · 2024Article
- NeoDesign: a computational tool for optimal selection of polyvalent neoantigen combinations.Bioinformatics (Oxford, England) · 2024Article
- Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics.Oncotarget · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease.Biochemistry · 2024Article
- Review
- CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation.Biomolecules · 2024Article
- Heterologous Expression and Purification of Eukaryotic ALA Synthase from E. coli.Methods in molecular biology (Clifton, N.J.) · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
The mitochondrion maintains and regulates its proteome with chaperones primarily inherited from its bacterial endosymbiont ancestor. Among these chaperones is the AAA+ unfoldase ClpX, an important regulator of prokaryotic physiology with poorly defined function in the eukaryotic mitochondrion. We observed phenotypic similarity in S. cerevisiae genetic interaction data between mitochondrial ClpX (mtClpX) and genes contributing to heme biosynthesis, an essential mitochondrial function. Metabolomic analysis revealed that 5-aminolevulinic acid (ALA), the first heme precursor, is 5-fold reduced in yeast lacking mtClpX activity and that total heme is reduced by half. mtClpX directly stimulates ALA synthase in vitro by catalyzing incorporation of its cofactor, pyridoxal phosphate. This activity is conserved in mammalian homologs; additionally, mtClpX depletion impairs vertebrate erythropoiesis, which requires massive upregulation of heme biosynthesis to supply hemoglobin. mtClpX, therefore, is a widely conserved stimulator of an essential biosynthetic pathway and uses a previously unrecognized mechanism for AAA+ unfoldases.
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What OpenQuestion holds
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.