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Mechanism of citrinin-induced dysfunction of mitochondria. IV--Effect on Ca2+ transport
G M Chagas1, M A Oliveira, A P Campello
1Departamento de Bioquímica da Universidade Federal do Paraná, Curitiba, Brasil.
Abstract:
The effect of citrinin on Ca2+ transport was studied in isolated kidney cortex and liver mitochondria, and baby hamster kidney cultured cells. The mycotoxin significantly inhibited the activity of 2-oxoglutarate and pyruvate dehydrogenases in both kidney cortex and liver mitochondria. Citrinin promoted a decrease in the velocity and in the total capacity of Ca2+ uptake, in both mitochondria. Apparently, citrinin acts by a mechanism similar to ruthenium red. In intact cultured cells, citrinin also had a preferential effect on mitochondrial Ca2+ fluxes. Citrinin promoted a marked decrease in the Ca2+ level in the mitochondrial matrix, whereas that of the extramitochondiral fraction became less affected. All the observed effects were dependent on the citrinin concentration.
Insights
Citrinin, a mycotoxin, disrupts cellular calcium (Ca2+) transport by inhibiting key enzymes and reducing mitochondrial Ca2+ uptake. These effects, observed in kidney and liver mitochondria and cultured cells, are concentration-dependent.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Citrinin is a mycotoxin with known nephrotoxic effects.
- Calcium (Ca2+) transport is crucial for mitochondrial function and cellular homeostasis.
- Mitochondria play a key role in regulating intracellular Ca2+ levels.
Purpose of the Study:
- To investigate the impact of citrinin on Ca2+ transport in kidney and liver mitochondria.
- To examine the effects of citrinin on Ca2+ fluxes in cultured cells.
- To elucidate the mechanism of citrinin's action on mitochondrial Ca2+.
Main Methods:
- Isolated kidney cortex and liver mitochondria were used.
- Baby hamster kidney (BHK) cultured cells were utilized.
- Enzyme activity assays and Ca2+ uptake measurements were performed.
Main Results:
- Citrinin significantly inhibited 2-oxoglutarate and pyruvate dehydrogenase activities in mitochondria.
- A decrease in the velocity and capacity of Ca2+ uptake was observed in mitochondria.
- Citrinin reduced mitochondrial matrix Ca2+ levels in intact cells, affecting extramitochondrial Ca2+ less.
Conclusions:
- Citrinin disrupts mitochondrial Ca2+ transport and homeostasis.
- The mycotoxin's action appears similar to ruthenium red, affecting mitochondrial Ca2+ uptake.
- Citrinin exerts concentration-dependent effects on cellular Ca2+ metabolism.