mito-QC illuminates mitophagy and mitochondrial architecture in vivo

  • J Cell Biol. 2016 Aug 1;214(3):333-45. doi: 10.1083/jcb.201603039.
Thomas G McWilliams  1 ,  Alan R Prescott  2 ,  George F G Allen  1 ,  Jevgenia Tamjar  1 ,  Michael J Munson  1 ,  Calum Thomson  3 ,  Miratul M K Muqit  4 ,  Ian G Ganley  5
Affiliations
  • 1. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • 2. Division of Cell Signalling and Immunology, University of Dundee, Dundee DD1 9SY, Scotland, UK Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • 3. Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • 4. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 9SY, Scotland, UK School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • 5. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 9SY, Scotland, UK [email protected].
PMID: 27458135 DOI: 10.1083/jcb.201603039
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.