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Site of action of the cord factor of Corynebacterium diphtheriae in mitochondria
Abstract:
Trehalose-6,6'-dicorynomycolate (T66DCM), the cord factor of Corynebacterium diphtheriae, induced in vitro a swelling accompanied with a partially irreversible change of the mitochondrial membrane system in mouse liver. Preincubation of the mitochondrial suspension with T66DCM resulted in an inhibition of phosphorylation coupled to the oxidation of either succinate or a number of reduced nicotinamide adenine dinucleotide-linked substrates and a loss of respiratory control. T66DCM affected both electron transport and phosphorylation at coupling site II and uncoupled respiration and phosphorylation at coupling site III. T66DCM stimulated mitochondrial adenosine triphosphatase. The induction of adenosine triphosphatase by T66DCM and by 2,4-dinitrophenol was additive.
Insights
Trehalose-6,6'-dicorynomycolate (T66DCM), a component of Corynebacterium diphtheriae, disrupts mouse liver mitochondrial function. This cord factor inhibits phosphorylation and respiratory control, while stimulating mitochondrial ATPase activity.
Area of Science:
- Mitochondrial biochemistry
- Cellular toxicology
Background:
- Trehalose-6,6'-dicorynomycolate (T66DCM) is the cord factor of Corynebacterium diphtheriae.
- Mitochondria are crucial for cellular energy production and are sensitive to toxins.
Purpose of the Study:
- To investigate the in vitro effects of T66DCM on mouse liver mitochondrial function.
- To elucidate the mechanisms by which T66DCM impacts mitochondrial respiration and phosphorylation.
Main Methods:
- Incubation of isolated mouse liver mitochondria with T66DCM.
- Measurement of phosphorylation, respiratory control, and ATPase activity.
Main Results:
- T66DCM induced mitochondrial swelling and irreversible membrane changes.
- Inhibition of phosphorylation coupled to substrate oxidation and loss of respiratory control.
- Uncoupling of respiration and phosphorylation at coupling site III and stimulation of mitochondrial ATPase.
Conclusions:
- T66DCM significantly impairs mitochondrial bioenergetics.
- The cord factor affects multiple sites within the mitochondrial electron transport chain and phosphorylation system.
- T66DCM exhibits toxic effects on mitochondrial membranes and function.