RT Journal Article
SR Electronic
T1 Heterogeneous Expression of Nuclear Encoded Mitochondrial Genes Distinguishes Inhibitory and Excitatory Neurons
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0232-21.2021
DO 10.1523/ENEURO.0232-21.2021
VO 8
IS 4
A1 Meghan E. Wynne
A1 Alicia R. Lane
A1 Kaela S. Singleton
A1 Stephanie A. Zlatic
A1 Avanti Gokhale
A1 Erica Werner
A1 Duc Duong
A1 Jennifer Q. Kwong
A1 Amanda J. Crocker
A1 Victor Faundez
YR 2021
UL http://www.eneuro.org/content/8/4/ENEURO.0232-21.2021.abstract
AB Mitochondrial composition varies by organ and their constituent cell types. This mitochondrial diversity likely determines variations in mitochondrial function. However, the heterogeneity of mitochondria in the brain remains underexplored despite the large diversity of cell types in neuronal tissue. Here, we used molecular systems biology tools to address whether mitochondrial composition varies by brain region and neuronal cell type in mice. We reasoned that proteomics and transcriptomics of microdissected brain regions combined with analysis of single-cell mRNA sequencing (scRNAseq) could reveal the extent of mitochondrial compositional diversity. We selected nuclear encoded gene products forming complexes of fixed stoichiometry, such as the respiratory chain complexes and the mitochondrial ribosome, as well as molecules likely to perform their function as monomers, such as the family of SLC25 transporters. We found that the proteome encompassing these nuclear-encoded mitochondrial genes and obtained from microdissected brain tissue segregated the hippocampus, striatum, and cortex from each other. Nuclear-encoded mitochondrial transcripts could only segregate cell types and brain regions when the analysis was performed at the single-cell level. In fact, single-cell mitochondrial transcriptomes were able to distinguish glutamatergic and distinct types of GABAergic neurons from one another. Within these cell categories, unique SLC25A transporters were able to identify distinct cell subpopulations. Our results demonstrate heterogeneous mitochondrial composition across brain regions and cell types. We postulate that mitochondrial heterogeneity influences regional and cell type-specific mechanisms in health and disease.