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Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity

Item Type:Article
Title:Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity
Creators Name:Fecher, C. and Trovò, L. and Müller, S.A. and Snaidero, N. and Wettmarshausen, J. and Heink, S. and Ortiz, O. and Wagner, I. and Kühn, R. and Hartmann, J. and Karl, R.M. and Konnerth, A. and Korn, T. and Wurst, W. and Merkler, D. and Lichtenthaler, S.F. and Perocchi, F. and Misgeld, T.
Abstract:Mitochondria vary in morphology and function in different tissues; however, little is known about their molecular diversity among cell types. Here we engineered MitoTag mice, which express a Cre recombinase-dependent green fluorescent protein targeted to the outer mitochondrial membrane, and developed an isolation approach to profile tagged mitochondria from defined cell types. We determined the mitochondrial proteome of the three major cerebellar cell types (Purkinje cells, granule cells and astrocytes) and identified hundreds of mitochondrial proteins that are differentially regulated. Thus, we provide markers of cell-type-specific mitochondria for the healthy and diseased mouse and human central nervous systems, including in amyotrophic lateral sclerosis and Alzheimer's disease. Based on proteomic predictions, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neuronal mitochondria. We also characterize cell-type differences in mitochondrial calcium buffering via the mitochondrial calcium uniporter (Mcu) and identify regulator of microtubule dynamics protein 3 (Rmdn3) as a determinant of endoplasmic reticulum-mitochondria proximity in Purkinje cells. Our approach enables exploring mitochondrial diversity in many in vivo contexts.
Keywords:Alzheimer Disease, Amyotrophic Lateral Sclerosis, Astrocytes, Brain, Calcium Signaling, Cerebellum, Cultured Cells, Fatty Acids, Mitochondria, Mitochondrial Membranes, Neurons, Proteomics, Purkinje Cells, Transgenic Mice, Animals, Mice
Source:Nature Neuroscience
ISSN:1097-6256
Publisher:Nature Publishing Group (U.S.A.)
Volume:22
Number:10
Page Range:1731-1742
Date:October 2019
Official Publication:https://doi.org/10.1038/s41593-019-0479-z
PubMed:View item in PubMed

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