Measuring in vivo mitophagy

By Nuo Sun, J. Yun, Jie Liu, D. Malide, Chengyu Liu, I. Rovira, Kira M. Holmström, M. Fergusson, Y. Yoo, C. Combs and 1 more. Molecules and Cells, 2015

602 citations recorded by the source corpus.

Summary Alterations in mitophagy have been increasingly linked to aging and age-related diseases. There are, however, no convenient methods to analyze mitophagy in vivo. Here, we describe a transgenic mouse model in which we expressed a mitochondrial-targeted form of the fluorescent reporter Keima (mt-Keima). Keima is a coral-derived protein that exhibits both pH-dependent excitation and resistance to lysosomal proteases. Comparison of a wide range of primary cells and tissues generated from the mt-Keima mouse revealed significant variations in basal mitophagy. In addition, we have employed the mt-Keima mice to analyze how mitophagy is altered by conditions including diet, oxygen availability, Huntingtin transgene expression, the absence of macroautophagy (ATG5 or ATG7 expression), an increase in mitochondrial mutational load, the presence of metastatic tumors and normal aging. The ability to assess mitophagy under a host of varying environmental and genetic perturbations suggests that the mt-Keima mouse should be a valuable resource.

Subfields: Epidemiology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/08509a4eb39c8fc742a2e4c2708bf19212c5431a

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Citations in the corpus

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. (2017, positive): “The use of a recently generated reporter mouse to assess in vivo mitophagy will shed light on how mitophagy flux is modulated in response to different genetic and pharmacological perturbations (Sun et al., 2015).”
Metabolic regulation of mitochondrial dynamics (2016, background): “The recent development of a mouse reporter for tracking mitophagy in vivo (Sun et al., 2015) will be helpful in this regard.”
Monitoring and Measuring Autophagy (2017, methodology): “In tissues from mt-Keima mice, for instance in the liver, dextran cascade blue (a fluorescent compound that accumulates in late endosomes and lysosomes) colocalizes with the Keima signal excited at 561 nm but not at 458 nm, confirming that the probes are delivered to the lysosome, thus reflecting mi”
Molecular mechanisms and physiological functions of mitophagy (2021, positive): “Similarly, the activity of mitophagy in specific brain region decreases during aging, as indicated by an in vivo study using transgenic mice expressing mt-Keima (Sun et al , 2015).”
Metabolic Control of Longevity. (2016, background): “Reducedmitophagy has also been associated with aging, at least in specific brain areas (Sun et al., 2015).”