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Fecher, C.* ; Trovò, L.* ; Müller, S.A.* ; Snaidero, N.* ; Wettmarshausen, J. ; Heink, S.* ; Ortiz, O. ; Wagner, I.* ; Kühn, R. ; Hartmann, J.* ; Karl, R.M.* ; Konnerth, A.* ; Korn, T.* ; Wurst, W. ; Merkler, D.* ; Lichtenthaler, S.F.* ; Perocchi, F. ; Misgeld, T.*

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

Nat. Neurosci. 22, 1731-1742 (2019)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cre Recombinase; Protein; Neurons; Mice; Uniporter; Dynamics; Energy; Mcu; Quantification; Peroxisomes
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Journal Nature Neuroscience
Quellenangaben Volume: 22, Issue: 10, Pages: 1731-1742 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Developmental Genetics (IDG)