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Extensive Ca2+ release from energized mitochondria induced by disulfiram
1Departamento de Bioquímica Instituto Nacional de Cardiología, Ignacio Chávez, México.
Journal of Bioenergetics and Biomembranes
|June 1, 1989
Summary
Disulfiram, an alcohol-deterrent drug, causes mitochondria to release accumulated calcium (Ca2+). This drug disrupts mitochondrial function, impacting membrane potential and swelling.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Mitochondria play a crucial role in cellular calcium homeostasis.
- Disulfiram is a medication used to deter alcohol consumption.
- The precise effects of disulfiram on mitochondrial function are not fully understood.
Purpose of the Study:
- To investigate the impact of disulfiram on mitochondrial calcium content.
- To elucidate the mechanisms by which disulfiram affects mitochondria.
Main Methods:
- Isolated mitochondria were treated with disulfiram (20 microM).
- Measurements included mitochondrial Ca2+ content, transmembrane potential (delta psi), and NAD(P)H/NAD(P) ratio.
- Effects were assessed in the presence and absence of Ca2+ accumulation and ruthenium red.
Main Results:
- Disulfiram induced a complete loss of accumulated mitochondrial Ca2+.
- This calcium release was associated with a collapse of the membrane potential, mitochondrial swelling, and decreased NAD(P)H/NAD(P) ratio.
- Disulfiram's effects were dependent on Ca2+ accumulation, and ruthenium red partially reversed these effects.
Conclusions:
- Disulfiram significantly disrupts mitochondrial Ca2+ regulation.
- The drug's action involves binding to mitochondrial sulfhydryl groups, affecting membrane integrity and function.
- These findings highlight a novel mechanism of disulfiram toxicity at the mitochondrial level.