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Updated: May 8, 2026
07:14
A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
La supresión de las interacciones mitocondria-retículo protege a los cardiomiocitos de lesiones letales por
Melanie Paillard1, Emily Tubbs, Pierre-Alain Thiebaut
1From INSERM UMR-1060, Laboratoire CarMeN, Université Lyon 1, Faculté de médecine Rockefeller et Charles Merieux Lyon-Sud, Lyon (M.P., E.T., P.T., L.G., C.C. Da S., G.T., N.M., E.B., A.D., M.A., J.R., M.O.); INSERM UMR-1046, Université Montpellier 1, Université Montpellier 2, CHU de Montpellier, Montpellier (J.F., A.L.); and Hospices Civils de Lyon, Hôpital Louis Pradel, Service d'Explorations Fonctionnelles Cardiovasculaires and CIC de Lyon, Lyon (N.M., M.O.), France.
Circulation
|August 29, 2013
Resumen
La ciclofilina D (CypD) interactúa con el complejo ER-mitocondria, mediando la transferencia de calcio. La inhibición de esta interacción protege a los cardiomiocitos de la lesión por hipoxia-reoxigenación al reducir la sobrecarga de calcio mitocondrial.
Área de la Ciencia:
- Cardiología Cardiología.
- Biología mitocondrial Biología mitocondrial
- Fisiología celular Fisiología celular.
Sus antecedentes:
- La transferencia de calcio (Ca2+) desde el retículo endoplasmático (ER) a las mitocondrias ocurre en los sitios de contacto de los orgánulos.
- El complejo VDAC1/Grp75/IP3R1 media en esta transferencia de Ca2+.
- La sobrecarga de Ca2+ mitocondrial activa la ciclofilina D (CypD), lo que lleva a la muerte celular a través de la apertura de los poros de la transición de permeabilidad, un factor conocido en la lesión de isquemia / reperfusión.
Objetivo del estudio:
- Para investigar el papel de la transferencia de Ca2+ de ER-mitocondrias en la muerte de los cardiomiocitos después de la hipoxia-reoxigenación.
- Para determinar si la vía de la ciclofilina D (CypD) está involucrada en este proceso.
Principales métodos:
- Investigó la interacción de la CypD con el complejo VDAC1/Grp75/IP3R1 en los cardiomiocitos.
- Utilizó la inhibición genética y farmacológica de CypD, IP3R1 y Grp75.
- Se examinaron los efectos de interrumpir la interacción ER-mitocondrias mediante la regulación a la baja de Mfn2.
- Contenido evaluado de Ca2+ mitocondrial y supervivencia celular bajo condiciones de hipoxia-reoxigenación.
Principales resultados:
- La CypD interactúa con el complejo VDAC1/Grp75/IP3R1 en los cardiomiocitos.
- La inhibición de la CypD redujo la transferencia de Ca2+ ER-mitocondria bajo condiciones normoxicas.
- Durante la hipoxia-reoxigenación, la interacción de CypD con el complejo aumentó con el contenido de Ca2+ mitocondrial.
- La inhibición de CypD, IP3R1, Grp75 o la interrupción de la interacción ER-mitocondrias atenuaron la sobrecarga de Ca2+ mitocondrial y las células protegidas.
Conclusiones:
- CypD juega un papel novedoso en la interfaz ER-mitocondria.
- La reducción de la interacción ER-mitocondrias durante la reperfusión protege a los cardiomiocitos de una lesión letal.
- Esta protección se logra mediante la disminución de la sobrecarga de Ca2+ mitocondrial a través del complejo CypD/VDAC1/Grp75/IP3R1.
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