Open Access
14 November 2017 Mitochondrial matrix pH as a decisive factor in neurometabolic imaging
Patrick M. Schaefer, Diana Hilpert, Moritz Niederschweiberer, Larissa Neuhauser, Sviatlana Kalinina, Enrico Calzia, Angelika Rueck, Bjoern von Einem, Christine A. F. von Arnim
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Abstract
Alterations of cellular bioenergetics are a common feature in most neurodegenerative disorders. However, there is a selective vulnerability of different brain regions, cell types, and even mitochondrial populations to these metabolic disturbances. Thus, the aim of our study was to establish and validate an in vivo metabolic imaging technique to screen for mitochondrial function on the subcellular level. Based on nicotinamide adenine dinucleotide (phosphate) fluorescence lifetime imaging microscopy [NAD(P)H FLIM], we performed a quantitative correlation to high-resolution respirometry. Thereby, we revealed mitochondrial matrix pH as a decisive factor in imaging NAD(P)H redox state. By combining both parameters, we illustrate a quantitative, high-resolution assessment of mitochondrial function in metabolically modified cells as well as in an amyloid precursor protein-overexpressing model of Alzheimer’s disease. Our metabolic imaging technique provides the basis for dissecting mitochondrial deficits not only in a range of neurodegenerative diseases, shedding light onto bioenergetic failures of cells remaining in their metabolic microenvironment.
CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Patrick M. Schaefer, Diana Hilpert, Moritz Niederschweiberer, Larissa Neuhauser, Sviatlana Kalinina, Enrico Calzia, Angelika Rueck, Bjoern von Einem, and Christine A. F. von Arnim "Mitochondrial matrix pH as a decisive factor in neurometabolic imaging," Neurophotonics 4(4), 045004 (14 November 2017). https://doi.org/10.1117/1.NPh.4.4.045004
Received: 14 August 2017; Accepted: 16 October 2017; Published: 14 November 2017
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CITATIONS
Cited by 31 scholarly publications.
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KEYWORDS
Fluorescence lifetime imaging

Oxygen

Neurophotonics

Proteins

Mode conditioning cables

Potassium

Luminescence

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