<i>mito</i>-QC illuminates mitophagy and mitochondrial architecture <i>in vivo</i>

Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities

miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation

MicroRNAs (miRNAs) have previously been implicated in a number of developmental processes, including development of the ventricular myocardium of the heart. To determine what, if any, additional roles miRNAs play in cardiogenesis, we deleted the miRNA-processing enzyme Dicer specifically in the developing murine heart. Embryos lacking cardiac Dicer lived longer than reported in previous studies using different alleles to remove cardiac Dicer activity and displayed a highly penetrant phenotype of double outlet right ventricle with a concurrent ventricular septal defect. Before the defect’s onset, Pitx2c and Sema3c, both required for outflow tract morphogenesis, were up-regulated in Dicer-deficient hearts. Interestingly, mesenchymal apoptosis in the outflow tract normally required for outflow tract alignment was greatly decreased in the mutants, likely contributing directly to the observed phenotype. In sum, we demonstrate here a specific developmental process, that of outflow tract morphogenesis, being hindered by the deletion of miRNAs during cardiogenesis