mito-QC illuminates mitophagy and mitochondrial architecture in vivo

J Cell Biol. 2016 Aug 1;214(3):333-45. doi: 10.1083/jcb.201603039. Epub 2016 Jul 25.

Abstract

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.

MeSH terms

  • Animals
  • Cerebellum / cytology
  • Embryo, Mammalian / cytology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Genes, Reporter
  • Kidney Cortex / cytology
  • Kidney Cortex / metabolism
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Mammals / metabolism
  • Mice, Transgenic
  • Mitochondria / metabolism*
  • Mitophagy*
  • Neurons / cytology
  • Neurons / metabolism
  • Organ Specificity