Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy.

ABSTRACT: The mitochondrial phosphate carrier (PiC) is critical for ATP synthesis by serving as the primary means for mitochondrial phosphate import across the inner membrane. In addition to its role in energy production, PiC is hypothesized to have a role in cell death as either a component or a regulator of the mitochondrial permeability transition pore (MPTP) complex. Here, we have generated a mouse model with inducible and cardiac-specific deletion of the Slc25a3 gene (PiC protein). Loss of PiC protein did not prevent MPTP opening, suggesting it is not a direct pore-forming component of this complex. However, Slc25a3 deletion in the heart blunted MPTP opening in response to Ca(2+) challenge and led to a greater Ca(2+) uptake capacity. This desensitization of MPTP opening due to loss or reduction

SUBMITTER: Kwong JQ 

PROVIDER: S-EPMC4085527 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature