ArticleBiochimica et biophysica acta. Molecular cell research2020
Molecular insights on cytochrome c and nucleotide regulation of apoptosome function and its implication in cancer.
Article in Biochimica et biophysica acta. Molecular cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- The Role of Apoptosis and Ferroptosis in Primary Mitochondrial Diseases: Mechanisms and Pathogenesis.International journal of molecular sciences · 2026Review
- Potential Antidote Against Lead Toxicity-A Review.International journal of molecular sciences · 2026Review
- Gallic Acid Potentiates Cisplatin Response in Cervical Cancer Cells Through Coordinated Cellular and Molecular Alterations.Biology · 2026Article
- Characterization of the interaction between human cytochromeMagnetic resonance letters · 2026Article
- Immune system, inflammatory response, and regulated cell death in breast cancer research (Review).Oncology reports · 2026Review
- Environmental light deprivation disrupts Leydig cell maturation and male reproductive development in rats.Scientific reports · 2025Article
- Enhanced Apoptosis in Melanoma Cells via Synergistic Action of Luteolin and 5-FU Through Oxidative Stress Modulation.Applied biochemistry and biotechnology · 2025Article
- Article
- Anticancer Nanoparticle Carriers of the Proapoptotic Protein CytochromePharmaceutics · 2025Review
- Methylglyoxal Formation-Metabolic Routes and Consequences.Antioxidants (Basel, Switzerland) · 2025Review
- Reversal of the tamoxifen‑resistant breast cancer malignant phenotype by proliferation inhibition with bromosulfonamidine amino‑podophyllotoxin.Oncology letters · 2024Article
- Environmental and Genetic Determinants of Ankylosing Spondylitis.International journal of molecular sciences · 2024Review
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- Diverse functions of cytochrome c in cell death and disease.Cell death and differentiation · 2024Review
- Cardiolipin Membranes Promote CytochromeMolecules (Basel, Switzerland) · 2024Article
- Review of Excessive Cytosolic DNA and Its Role in AIM2 and cGAS-STING Mediated Psoriasis Development.Clinical, cosmetic and investigational dermatology · 2024Review
- Advances in exercise to alleviate sarcopenia in older adults by improving mitochondrial dysfunction.Frontiers in physiology · 2023Review
- Cytochrome c in cancer therapy and prognosis.Bioscience reports · 2022Article
- Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats.Biological research · 2022Article
- The MreA Metal-Binding Sites C40, H65, and C69 Play a Critical Role in the Metal Tolerance of Pseudomonas putida KT2440.Current microbiology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome c (Cyt c) released from mitochondria interacts with Apaf-1 to form the heptameric apoptosome, which initiates the caspase cascade to execute apoptosis. Although lysine residue at 72 (K72) of Cyt c plays an important role in the Cyt c-Apaf-1 interaction, the underlying mechanism of interaction between Cyt c and Apaf-1 is still not clearly defined. Here we identified multiple lysine residues including K72, which are also known to interact with ATP, to play a key role in Cyt c-Apaf-1 interaction. Mutation of these lysine residues abrogates the apoptosome formation causing inhibition of caspase activation. Using in-silico molecular docking, we have identified Cyt c-binding interface on Apaf-1. Although mutant Cyt c shows higher affinity for Apaf-1, the presence of Cyt c-WT restores the apoptosome activity. ATP addition modulates only mutant Cyt c binding to Apaf-1 but not WT Cyt c binding to Apaf-1. Using TCGA and cBioPortal, we identified multiple mutations in both Apaf-1 and Cyt c that are predicted to interfere with apoptosome assembly. We also demonstrate that transcript levels of various enzymes involved with dATP or ATP synthesis are increased in various cancers. Silencing of nucleotide metabolizing enzymes such as ribonucleotide reductase subunit M1 (RRM1) and ATP-producing glycolytic enzymes PKM2 attenuated ATP production and enhanced caspase activation. These findings suggest important role for lysine residues of Cyt c and nucleotides in the regulation of apoptosome-dependent apoptotic cell death as well as demonstrate how these mutations and nucleotides may have a pivotal role in human diseases such as cancer.
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Registered trials
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