期刊
NATURE NEUROSCIENCE
卷 22, 期 10, 页码 1731-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41593-019-0479-z
关键词
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资金
- Deutsche Forschungsgemeinschaft through the Munich Center for Systems Neurology (SyNergy) [EXC 1010]
- Center for Integrated Protein Science Munich [EXC 114]
- Emmy-Noether program of the Deutsche Forschungsgemeinschaft [Pe2053/1-1]
- European Research Council under the European Union [FP/2007-2013, CoG 616791, CoG 647215]
- German Center for Neurodegenerative Diseases (DZNE Munich)
- EMBO Long-Term Fellowship [EMBO ALTF 108-2013]
- Centers of Excellence in Neurodegeneration
- Helmholtz-Israel Program
- Swiss National Science Formation
- HHS Foundation
- German Federal Ministry of Education and Research (BMBF) through 'T-B interaction in NMO'
- German Federal Ministry of Education and Research (BMBF) through 'Mitochondrial endophenotypes of Morbus Parkinson' [031A430E]
- Senior Hertie Professorship of Neuroscience
- Institute for Advanced Study, Technical University of Munich (Focus Group 'Subcellular Dynamics in Neurons')
- [CRC870]
- [CRC1054]
- [CRC-TR128]
- [FOR2290]
- [Mi694/7-1/8-1]
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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