A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts.

ABSTRACT: We performed global gene expression analyses in mouse hearts with progressive respiratory chain deficiency and found a metabolic switch at an early disease stage. The tissue-specific mitochondrial transcription factor A (Tfam) knockout mice of this study displayed a progressive heart phenotype with depletion of mtDNA and an accompanying severe decline of respiratory chain enzyme activities along with a decreased mitochondrial ATP production rate. These characteristics were observed after 2 weeks of age and became gradually more severe until the terminal stage occurred at 10-12 weeks of age. Global gene expression analyses with microarrays showed that a metabolic switch occurred early in the progression of cardiac mitochondrial dysfunction. A large number of genes encoding critical enzymes

SUBMITTER: Hansson A 

PROVIDER: S-EPMC365756 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature