Quantitative analysis of neuronal mitochondrial movement reveals patterns resulting from neurotoxicity of rotenone and 6-hydroxydopamine

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Simões, Rui F
Pino, Rute
Moreira-Soares, Maurício
Kovarova, Jaromira
Neuzil, Jiri
Travasso, Rui
Oliveira, Paulo J
Cunha-Oliveira, Teresa
Pereira, Francisco B
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2021
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Abstract

Alterations in mitochondrial dynamics, including their intracellular trafficking, are common early manifestations of neuronal degeneration. However, current methodologies used to study mitochondrial trafficking events rely on parameters that are primarily altered in later stages of neurodegeneration. Our objective was to establish a reliable applied statistical analysis to detect early alterations in neuronal mitochondrial trafficking. We propose a novel quantitative analysis of mitochondria trajectories based on innovative movement descriptors, including straightness, efficiency, anisotropy, and kurtosis. We evaluated time- and dose-dependent alterations in trajectory descriptors using biological data from differentiated SH-SY5Y cells treated with the mitochondrial toxicants 6-hydroxydopamine and rotenone. MitoTracker Red CMXRos-labelled mitochondria movement was analyzed by total internal reflection fluorescence microscopy followed by computational modelling to describe the process. Based on the aforementioned trajectory descriptors, this innovative analysis of mitochondria trajectories provides insights into mitochondrial movement characteristics and can be a consistent and sensitive method to detect alterations in mitochondrial trafficking occurring in the earliest time points of neurodegeneration.

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FASEB Journal

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35

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12

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© 2021 Federation of American Societies for Experimental Biology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.

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Biochemistry and cell biology

Medical physiology

exploratory data analysis

live cell imaging

mitochondria movement

neurotoxicants

principal component analysis

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Simões, RF; Pino, R; Moreira-Soares, M; Kovarova, J; Neuzil, J; Travasso, R; Oliveira, PJ; Cunha-Oliveira, T; Pereira, FB, Quantitative analysis of neuronal mitochondrial movement reveals patterns resulting from neurotoxicity of rotenone and 6-hydroxydopamine, FASEB Journal, 2021, 35 (12), pp. e22024

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