Cytochrome b (encoded by MT-CYB) is a mitochondrial DNA-encoded protein that forms the core of Complex III (Cytochrome bc1 complex) in the electron transport chain. It plays a critical role in oxidative phosphorylation and mitochondrial function, with implications for neurodegenerative diseases.
| Cytochrome b (MT-CYB) |
|---|
| Gene | [MT-CYB](/genes/mt-cyb) (mitochondrial) |
| UniProt | [P00156](https://www.uniprot.org/uniprot/P00156) |
| Molecular Weight | ~42.5 kDa |
| Subcellular Localization | Mitochondrial inner membrane |
| Protein Family | Cytochrome b family |
Cytochrome b is a key component of Complex III (ubiquinol-cytochrome c reductase), which catalyzes the transfer of electrons from ubiquinol to cytochrome c. This process generates a proton gradient across the mitochondrial inner membrane, driving ATP synthesis.
- Electron Transfer: Cytochrome b contains two heme b groups (bH and bL) that facilitate electron transfer
- Q Cycle: Involved in the bifurcated electron transfer mechanism (Q cycle)
- Proton Pumping: Contributes to proton translocation across the inner membrane
- Expressed in neurons and glial cells
- Essential for neuronal energy metabolism
- Critical for maintaining mitochondrial membrane potential
- Mitochondrial dysfunction is an early event in AD pathogenesis
- Complex III activity is reduced in AD brains
- Cytochrome b mutations may contribute to amyloid-beta toxicity
- MT-CYB variants have been associated with PD risk
- Complex I deficiency is well-documented in PD, but Complex III dysfunction also contributes
- PINK1 and Parkin regulate mitochondrial quality, which affects cytochrome b function
¶ ALS and Other Neurodegenerative Diseases
- Mitochondrial dysfunction is a common feature
- Cytochrome b mutations can cause mitochondrial myopathy
- Energy failure contributes to neurodegeneration
- Coenzyme Q10 (CoQ10): Electron carrier that can bypass Complex III dysfunction
- Mitochondrial antioxidants: Target oxidative stress from electron leak
- Gene therapy: Potential for mtDNA delivery
- Mitochondrial replacement therapy
- Small molecules targeting bc1 complex
- mtDNA heteroplasmy modulation
- Mitochondrial complex III deficiency in Alzheimer's disease (2020)
- MT-CYB variants and Parkinson's disease risk (2019)
- Cytochrome bc1 complex as therapeutic target (2021)