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Interaction of MCU with Miro1 regulates mitochondrial functions in neurons

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Title
Interaction of MCU with Miro1 regulates mitochondrial functions in neurons
Author
Hong, Ki Do
Advisor
Min, Kyung Tai
Issue Date
2020-08
Publisher
Graduate School of UNIST
Abstract
Mitochondrial calcium (Ca2+) uptake is critical for regulating energy metabolism and mitochondrial movement, as well as buffering of intracellular Ca2+. This Ca2+ uptake is mediated by a highly selective Ca2+ pore complex composed of mitochondrial calcium uniporter (MCU), the inner mitochondrial membrane protein, and its regulatory proteins. Although the mechanism how MCU and its regulatory components regulate mitochondrial Ca2+ uptake is well established, a mechanism underlying the regulation of mitochondrial movement by MCU still remain unrevealed. Our previous work found mitochondrial Ca2+ content mediated by MCU is a critical factor for regulating the mitochondrial mobility in axon. Here, we find MCU interacts with mitochondrial Rho GTPase 1 (Miro1), known to regulate the mitochondrial mobility. We identify MCU’s N-terminal domain, previously known as mitochondrial targeting sequence (MTS), is essential for interaction with Miro1. Our results reveal N-terminus of MCU contains a potential transmembrane domain that makes it possible to interact with Miro1, however, is not required for the localization of MCU into mitochondria. Furthermore, our data shows the elevation of intracellular Ca2+ triggers the cleavage of N-terminal domain of MCU, altering the interaction with Miro1, and this Ca2+-dependent MCU-Miro1 interaction is necessary to facilitate the axonal mitochondrial mobility. Together, our findings reveal a novel functional relationship between Miro1 and MCU as a new component of the MCU complex, and a new regulator of mitochondrial movement, respectively.
Description
Department of Biological Sciences
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