mito-QC illuminates mitophagy and mitochondrial architecture in vivo

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 to...

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Bibliographic Details
Published in:The Journal of cell biology 2016-08, Vol.214 (3), p.333-345
Main Authors: McWilliams, Thomas G, Prescott, Alan R, Allen, George F G, Tamjar, Jevgenia, Munson, Michael J, Thomson, Calum, Muqit, Miratul M K, Ganley, Ian G
Format: Article
Language:English
Subjects:
Animals
Autophagy
Cellular biology
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
Microscopy
Mitochondria
Mitochondria - metabolism
Mitophagy
Neurons - cytology
Neurons - metabolism
Organ Specificity
Pathology
Physiology
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201603039