Target intelligence / Profile preview

Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 (UQCRFS1)

Target
UQCRFS1
Molecular classification
Enzyme, Respiratory chain protein, Iron-sulfur protein, Mitochondrial Complex III subunit
01

Overview

Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 (UQCRFS1) is a nuclear-encoded protein that serves as a key subunit of mitochondrial complex III (cytochrome b-c1 complex) in the electron transport chain. UQCRFS1 contains a [2Fe-2S] Rieske iron-sulfur cluster and cycles between two conformational states to transfer electrons from ubiquinol to cytochrome c1, linking redox reactions to proton translocation and energy production. It is critical for complex III assembly and function; disruptions can lead to metabolic disease, and its amplification is associated with aggressive cancers.

Other names
Cytochrome b-c1 complex subunit Rieske, mitochondrialRieske iron-sulfur proteinCytochrome b-c1 complex subunit 5Complex III subunit 5Cytochrome b-c1 complex subunit 9UQCRFS1 MTSRIS1RIP1RISPUQCR5
02

Mechanism of action

Inhibition or modulation of electron transport in mitochondrial complex III impairs ATP production and induces cell death, especially in cells reliant on oxidative phosphorylation (e.g., some cancer cells)

03

Biological functions

Electron transportMitochondrial ATP synthesisOxidative phosphorylationRedox activity (oxidoreductase)
04

Disease associations

Cancer (especially aggressive breast cancers, acute myeloid leukemia)Mitochondrial complex III deficiencyLactic acidosis
05

Safety considerations

Mitochondrial toxicityInduction of lactic acidosis and metabolic compromiseOff-target effects on non-tumor tissues reliant on mitochondrial ATP generation
06

Interacting drugs

Antineoplastic agents and mitochondrial complex III inhibitors such as antimycin A are known to target complex III, within which UQCRFS1 is a subunit. Specific drugs directly targeting UQCRFS1 for clinical use are currently limited.
07

Biomarkers

Amplification of UQCRFS1 gene in tumor tissue (breast cancer, AML)Mutations or deficient expression in mitochondrial disorders (Complex III deficiency)

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