A Prototypical Small-Molecule Modulator Uncouples Mitochondria in Response to Endogenous Hydrogen Peroxide Production

نویسندگان

  • Stephen J McQuaker
  • Casey L Quinlan
  • Stuart T Caldwell
  • Martin D Brand
  • Richard C Hartley
چکیده

A high membrane potential across the mitochondrial inner membrane leads to the production of the reactive oxygen species (ROS) implicated in aging and age-related diseases. A prototypical drug for the correction of this type of mitochondrial dysfunction is presented. MitoDNP-SUM accumulates in mitochondria in response to the membrane potential due to its mitochondria-targeting alkyltriphenylphosphonium (TPP) cation and is uncaged by endogenous hydrogen peroxide to release the mitochondrial uncoupler, 2,4-dinitrophenol (DNP). DNP is known to reduce the high membrane potential responsible for the production of ROS. The approach potentially represents a general method for the delivery of drugs to the mitochondrial matrix through mitochondria targeting and H(2)O(2)-induced uncaging.

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عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2013