Cytochrome C contains a heme group covalently bound via thioether linkages to cysteine residues. The iron in heme cycles between Fe2+ (reduced) and Fe3+(oxidized) states during electron transfer. It acts as a mobile electron shuttle in the mitochondrial electron transport chain. It acts as a pro-apoptotic signal when released from mitochondria.
Cytochrome C
| CAS No: | 9007-43-6 |
| EINECS No: | 232-700-1 |
| EC No: | 232-700-8 |
| Synonyms: | CYC, Cytochrome C oxidase substrate, Cyt C, ferrocytochrome C, ferricytochrome C |
Product Summary
Cytochrome C is a highly conserved, heme-containing mitochondrial protein essential in both electron transport and apoptotic signaling. With a molecular weight around 12.4 kDa, it functions by transferring electrons between respiratory complexes III and IV as well as activates caspases upon release into the cytosol. It is widely used in biochemistry, cell biology, and molecular medicine research. Its versatility in oxidative and apoptotic pathways makes it a powerful tool in studies of cell death, mitochondrial disorders, drug screening, and ROS biology.
Function
Mechanism of Action
- Electron Carrier: In mitochondrial oxidative phosphorylation, Cytochrome C shuttles electrons from complex III (cytochrome bc₁ complex) to complex IV (Cytochrome C oxidase), generating a proton gradient across the inner mitochondrial membrane. This drives ATP production by enabling proton pumping.
- Pro-apoptotic Trigger: When mitochondrial outer membrane is permeabilized (e.g., by Bax/Bak), Cytochrome C leaks into the cytosol. It then binds to Apaf-1 and procaspase-9, forming the apoptosome → activation of downstream caspases → programmed cell death.
Optimal conditions: pH 6.0–7.5, temperature 25–37 °C.
Applications in Scientific Research
- Apoptosis research: Cytochrome C release is a key marker of mitochondrial-mediated apoptosis.
- Bioenergetics and electron transport chain (ETC) studies.
- Mitochondrial dysfunction models (neurodegenerative diseases, cancer).
- Protein–protein interaction assays (e.g., binding to Apaf-1).
- Used as spectrophotometric standards: Due to distinct absorbance at 550 nm (reduced form).
- Oxidoreductase enzyme assays: Often used as a substrate for Cytochrome C oxidase (complex IV) or superoxide dismutase tests.
- Drug screening: Assessing effects of compounds on apoptosis or mitochondrial function.
- ROS generation models: Cytochrome C can generate ROS under certain conditions.
- Artificial electron transfer systems in bioelectronic and electrochemical studies.
Packaging & Storage
- Sources: purified from heart tissue of horse (equine), bovine, or porcine
- Available as reddish or red-brown crystalline powder
- Store in an airtight container, protected from light, in a cool and dry place.
References
- Alvarez-Paggi D, et al. 2017: Multifunctional cytochrome c: learning new tricks from an old dog, Chem Rev. 17(21): 13382–460.
- Hannibal L, et al. 2016: Alternative conformations of cytochrome c: Structure, function, and detection, Biochemistry 55(3): 407–28.
- Bayir H, et al. 2006: Apoptotic interactions of cytochrome c: redox flirting with anionic phospholipids within and outside of mitochondria, Biochim Biophys Acta. 1757(5-6): 648–59.
- Kruglik S G, et al. 2017: Structural changes and picosecond to second dynamics of cytochrome c in interaction with nitric oxide in ferrous and ferric redox states, Phys Chem Chem Phys. 19(32): 21317–34.
- Scharlau M, et al. 2019: Definition of the interaction domain and electron transfer route between cytochrome c and cytochrome oxidase, Biochemistry 58(40): 4125–35.
- Kalpage H A, et al. 2020: Cytochrome c phosphorylation: Control of mitochondrial electron transport chain flux and apoptosis, Int J Biochem Cell Biol. 121: 105704.
- Kalpage H A, et al. 2020: Brain-specific serine-47 modification of cytochrome c regulates cytochrome c oxidase activity attenuating ROS production and cell death: Implications for ischemia/reperfusion injury and Akt signaling, Cells 9(8): 1843.
- Hüttemann M, et al. 2012: Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation, Biochim Biophys Acta. 1817(4): 598–609.
- Kranz R G, et al. 2009: Cytochrome c biogenesis: mechanisms for covalent modifications and trafficking of heme and for heme-iron redox control, Microbiol Mol Biol Rev. 73(3): 510–28.
- Santucci R, et al. 2019: Cytochrome c: An extreme multifunctional protein with a key role in cell fate, Int J Biol Macromol. 136: 1237–46.
- Jiang X, Wang X. 2004: Cytochrome C-mediated apoptosis, Annu Rev Biochem. 73: 87–106.
- Delinois L J, et al. 2021: Cytochrome c: Using biological insight toward engineering an optimized anticancer biodrug, Inorganics (Basel). 9(11): 83.