Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis program via induction of NF-E2-related factor (Nrf)2 gene expression and nuclear...

The thermogenic peroxisome proliferator-activated receptor gamma (PPAR-gamma) coactivator 1 (PGC-1) has previously been shown to activate mitochondrial biogenesis in part through a direct interaction with nuclear respiratory factor 1 (NRF-1). In order to identify related coactivators that act through NRF-1, we searched the databases for sequences with similarities to PGC-1. Here, we describe th...

Rationale: Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia. Objective: We examined the hypothesis that EPO receptor (EpoR) ligand-binding, which activates endothelial NO synthase...

Apoptosis is a component of cardiac remodeling following myocardial ischemia and infarction. MicroRNAs (miRNAs) are involved in regulating a range of cellular biological processes, including apoptosis, by regulating gene expression at the post-transcriptional level. Nuclear respiratory factor-1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins...

IMPORTANCE The important depletion of mitochondrial DNA (mtDNA) and the general depression of mitochondrial respiratory chain complex levels (including complex II) have been confirmed, implying an increasing paucity of mitochondria in the muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I, -II, and -III, respectively). OBJECTIVE To investigate mitochondrial dysfunct...