Meclizine rescues cardiac function and mitochondrial ultrastructure by ATP- and glycolysis-independent mechanisms in a genetic model of mitochondrial energy dysfunction.

ABSTRACT: Primary mitochondrial cardiomyopathies are an unmet clinical challenge, as there are no therapies that directly address the underlying mitochondrial dysfunction. We previously reported that the cardiomyocyte-specific deletion of the mitochondrial phosphate carrier (SLC25A3), which imports phosphate required for ATP synthesis, produces a model of mitochondrial cardiomyopathy in which total cardiac ATP levels are preserved despite defective mitochondrial ATP production. This was accompanied by increased glycolytic activity and reduced mitochondrial flux, leading us to hypothesize that pharmacologically enhancing glycolysis might be protective when the mitochondrial energy machinery is intrinsically impaired. To test this, we turned to meclizine, an FDA-approved antihistamine previously shown

SUBMITTER: Ghazal N 

PROVIDER: S-EPMC12424673 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature