title: Measuring In Vivo Mitophagy.
abstract: 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.
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Nuo
authors.initials: N
authors.lastname: Sun
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Light Microscopy Core, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Malide
authors.affiliation: Transgenic Core, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Ilsa I
authors.initials: II
authors.lastname: Rovira
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Kira M
authors.initials: KM
authors.lastname: Holmström
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Fergusson
authors.affiliation: Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Light Microscopy Core, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Combs
authors.affiliation: Center for Molecular Medicine, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA. Electronic address: finkelt@nih.gov.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D063306:Mitophagy; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D010100:Oxygen