ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human mitochondrial holocytochrome c synthase's heme binding, maturation determinants, and complex formation with cytochrome c.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 52 citations in OpenAlex.
- Revisiting LSDMCA: male lethality escape and genotype-phenotype correlations.European journal of human genetics : EJHG · 2026Article
- Inhibitors of cytochromemBio · 2026Article
- Structural Basis of a Novel Heme Binding Bacterial One-Component Switch.bioRxiv : the preprint server for biology · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Multi-omics landscape and functional validation of HCCS in breast cancer: from pan-cancer immunometabolic characterization to regulating tumor proliferation.Frontiers in genetics · 2026Article
- FAM136A depletion induces mitochondrial stress and reduces mitochondrial membrane potential and ATP production.FEBS open bio · 2025Article
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- HCCS Serves as Potential Prognostic Biomarker and Therapeutic Target in Human Breast Cancer.International journal of breast cancer · 2025Article
- Article
- Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels.Drug discovery today · 2024Review
- Structural Insights into Mechanisms Underlying Mitochondrial and Bacterial Cytochrome c Synthases.Biomolecules · 2024Article
- Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024Article
- Oxidative protein folding in the intermembrane space of human mitochondria.FEBS open bio · 2024Review
- Full-length GSDME mediates pyroptosis independent from cleavage.Nature cell biology · 2024Article
- Recurrent evolutionary switches of mitochondrial cytochrome c maturation systems in Archaeplastida.Nature communications · 2024Article
- Recombinant Biogenesis and Analysis of Cytochrome c Species.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Protein N-myristoylation plays a critical role in the mitochondrial localization of human mitochondrial complex I accessory subunit NDUFB7.Scientific reports · 2023Article
- Structural basis of membrane machines that traffick and attach heme to cytochromes.The Journal of biological chemistry · 2023Article
- Genetically Encoded Fluorescent Probe for Detection of Heme-Induced Conformational Changes in Cytochrome c.Biosensors · 2023Article
- Transition metal ions and neurotransmitters: coordination chemistry and implications for neurodegeneration.RSC chemical biology · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Proper functioning of the mitochondrion requires the orchestrated assembly of respiratory complexes with their cofactors. Cytochrome c, an essential electron carrier in mitochondria and a critical component of the apoptotic pathway, contains a heme cofactor covalently attached to the protein at a conserved CXXCH motif. Although it has been known for more than two decades that heme attachment requires the mitochondrial protein holocytochrome c synthase (HCCS), the mechanism remained unknown. We purified membrane-bound human HCCS with endogenous heme and in complex with its cognate human apocytochrome c. Spectroscopic analyses of HCCS alone and complexes of HCCS with site-directed variants of cytochrome c revealed the fundamental steps of heme attachment and maturation. A conserved histidine in HCCS (His154) provided the key ligand to the heme iron. Formation of the HCCS:heme complex served as the platform for interaction with apocytochrome c. Heme was the central molecule mediating contact between HCCS and apocytochrome c. A conserved histidine in apocytochrome c (His19 of CXXCH) supplied the second axial ligand to heme in the trapped HCCS:heme:cytochrome c complex. We also examined the substrate specificity of human HCCS and converted a bacterial cytochrome c into a robust substrate for the HCCS. The results allow us to describe the molecular mechanisms underlying the HCCS reaction.
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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.