Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions

Area of Science:

• Biochemistry
• Toxicology
• Mitochondrial Biology

Background:

• Mitochondrial thioredoxin reductase (TrxR) is crucial for cellular redox homeostasis.
• Various metal compounds, including gold complexes, are known to interact with biological systems.
• Understanding the specific targets and effects of these compounds is vital for assessing their biological impact.

Purpose of the Study:

• To investigate the inhibitory effects of gold(I) and gold(III) complexes, other metal ions, and metal complexes on mitochondrial thioredoxin reductase.
• To evaluate the impact of these compounds on mitochondrial functions, including respiration and membrane potential.
• To determine the specificity of gold compounds compared to other metal-based agents.

Main Methods:

• Assessed the inhibitory activity of various gold complexes, metal ions (zinc, cadmium), and metal complexes (cisplatin, zinc pyrithione, tributyltin) on mitochondrial thioredoxin reductase.
• Measured IC(50) values to quantify enzyme inhibition.
• Examined the effects on mitochondrial functions such as respiratory chain activity, membrane potential, and swelling.

Main Results:

• Gold(I) and gold(III) complexes were potent inhibitors of mitochondrial thioredoxin reductase (IC(50) 0.020–1.42 µM).
• Other metal ions and complexes showed significantly less inhibition of thioredoxin reductase (IC(50) 11.8–76.0 µM).
• Gold compounds minimally affected the mitochondrial respiratory chain, whereas other metal complexes induced marked inhibition, decreased membrane potential, and caused swelling.

Conclusions:

• Gold compounds are highly specific inhibitors of mitochondrial thioredoxin reductase.
• This specific inhibition by gold compounds influences other cellular functions, such as membrane permeability.
• Non-gold metal ions and complexes exhibit lower specificity, targeting multiple mitochondrial functions.