Mitochondrial transport proteins RHOT1 and RHOT2 serve as docking sites for PRKN-mediated mitophagy

Autophagy
Dzhamilja SafiulinaAllen Kaasik

Abstract

The Parkinson disease-associated proteins PINK1 and PRKN coordinate the ubiquitination of mitochondrial outer membrane proteins to tag them either for degradation or for autophagic clearance of the mitochondrion. The proteins include the mitochondrial trafficking proteins RHOT1 and RHOT2, the removal of which may be required for immobilization of mitochondria prior to mitophagy. Here, we demonstrate that RHOT1 and RHOT2 are not only substrates for PINK1-PRKN-dependent degradation but that they also play an active role in the process of mitophagy. RHOT1, and likely also RHOT2, may act as a docking site for inactive PRKN prior to mitochondrial damage, thus keeping PRKN in close proximity to its potential substrates and thereby facilitating mitophagy. We also show that RHOT1 functions as a calcium-sensing docking site for PRKN, and we suggest that calcium binding to RHOT is a key step in the calcium-dependent activation of mitophagy machinery.

References

Jan 1, 2010·Frontiers in Synaptic Neuroscience·Victoria F SafiulinaEnrico Cherubini

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Citations

Jan 5, 2020·Cell Death and Differentiation·Ying Yang, Daniel J Klionsky
Jun 19, 2021·Critical Reviews in Biochemistry and Molecular Biology·Zuzana NahackaJiri Neuzil
Jan 20, 2022·American Journal of Physiology. Cell Physiology·Rakesh Kumar SharmaGiulia Bertolin

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Methods Mentioned

BETA
ubiquitination
GTPases
involve

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