Abstract
Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. This method allows the visualization of in vivo astrocyte- endothelial cell (EC) and astrocyte-pericyte IMT. We demonstrate evidence of astrocyte-EC and astrocyte-pericyte mitochondrial transfer within brain capillaries. We also show that healthy aging enhances mitochondrial transfer from astrocytes to brain capillaries, revealing a potential link between brain aging and cellular mitochondrial dynamics. Finally, we observe that astrocyte-derived extracellular vesicles transfer mitochondria to brain microvascular endothelial cells, showing the potential route of in vivo IMT. These results represent a breakthrough in our understanding of IMT in the brain and a new target in brain aging and neurovascular metabolism.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1177/0271678X241306054
Funding Information
The author(s) disclosed receipt of the following financial sup- port for the research, authorship, and/or publication of this article: The studies were supported by NIH P20 GM148326 (PGS/WBH). This research was supported in part by IK2 BX004618 (WBH) from BLR&D of the Department of Veterans Affairs and HT9425-24-1-0301 from the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense Epilepsy Research Program. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States government.
Repository Citation
Velmurugan, Gopal V.; Vekaria, Hemendra J.; Patel, Samir P.; Sullivan, Patrick G.; and Hubbard, W. Brad, "Astrocytic mitochondrial transfer to brain endothelial cells and pericytes in vivo increases with aging" (2024). Neurology Faculty Publications. 104.
https://uknowledge.uky.edu/neurology_facpub/104
Notes/Citation Information
© The Author(s) 2024