Resumen
La membrana mitocondrial externa desempeña un papel crucial en la regulación del metabolismo energético en las células aeróbicas al controlar el intercambio de diversos metabolitos cargados e iones inorgánicos a través de sus canales aniónicos dependientes de voltaje (voltage-dependent anion channels, VDAC). Se han propuesto diversos mecanismos para la generación del potencial de membrana externa (OMP). Uno de ellos, el mecanismo VDAC-hexoquinasa (VDAC-HK), permitió explicar los efectos Warburg y Crabtree como resultado de una supresión eléctrica de las mitocondrias por el OMP dependiente del metabolismo. Se propone aquí un nuevo mecanismo, el VDAC-glicerol quinasa (VDAC-GK), para la generación del OMP, considerando que la glicerol quinasa compite con la hexoquinasa por el mismo sitio de unión en los VDAC. El modelo computacional desarrollado demostró la posibilidad de generar el OMP. La magnitud del OMP predicha por el modelo depende de las concentraciones intracelulares de glicerol y glicerol-3-fosfato. Según el análisis termodinámico, un OMP positivo relativamente alto, generado por los complejos VDAC-GK, debería acelerar la oxidación del glicerol-3-fosfato externo por acción de la glicerol-3-fosfato deshidrogenasa (GPD2), localizada en el lado externo de la membrana mitocondrial interna. Las posibles funciones fisiológicas y fisiopatológicas del OMP generado en la regulación del metabolismo celular a través de la «encrucijada eléctrica» del metabolismo lipídico, la glucólisis y la fosforilación oxidativa, constituyen temas para futuros estudios experimentales.
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