Effects of alpha-mangostin on mitochondrial energetic metabolism.
Although alpha-mangostin prevents from toxicity associated to oxidative stress, it also promotes apoptotic cell death in cancer cells. Such effects have been associated with mitochondrial membrane depolarization and cytochrome c release. Therefore, the aim of this work was to analyze the potentially harmful effect of this natural compound on relevant parameters of mitochondrial function from normal tissue. Our results showed that alpha-mangostin protected mitochondria from peroxidative damage, but at high concentration, it acted as an uncoupler, reduced dramatically ADP-stimulated respiration and inhibited the activity of respiratory complex IV, making mitochondria prone to permeability transition, which is a mitochondrial player on cell fate.
Martínez-Abundis
E
E
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1., Col. Sección XVI, Mexico 14080, D.F., Mexico.
García
N
N
Correa
F
F
Hernández-Reséndiz
S
S
Pedraza-Chaverri
J
J
Zazueta
C
C
D000818:Animals; D017209:Apoptosis; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004734:Energy Metabolism / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D051336:Mitochondrial Membranes / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D014475:Uncoupling Agents / Q000633:toxicity*; D044004:Xanthones / Q000633:toxicity*
D014475:Uncoupling Agents; D044004:Xanthones; D003576:Electron Transport Complex IV; C021053:mangostin