Objective: The objective of this study is to explore how Parkin modulates the interplay between mitochondria and the endoplasmic reticulum (ER), along with elucidating its underlying mechanisms.The objective of this study is to explore how Parkin modulates the interplay between mitochondria and the endoplasmic reticulum (ER), along with elucidating its underlying mechanisms.
Background: Accumulating evidence shows that the inter-organelle connection between mitochondria and ER, known as the mitochondria-associated ER membrane (MAM), plays a crucial role in Parkinson’s disease (PD) pathogenesis. Parkin is partly distributed in the MAM. However, the modulation and mechanism of Parkin regarding MAM remain elusive.
Method: In this study, we analyzed the interaction between mitochondria and ER) in Parkin knockout (KO) and control M17 cells, employing live-cell imaging to observe calcium flux. The interaction between Parkin and MAM tethering proteins was explored using mass spectrometry and immunoprecipitation. Meanwhile, subcellular fractionation was conducted to isolate MAM components, and the impact of Parkin KO on interacting proteins was analyzed. Ultimately, the ubiquitination modulation of MAM components by parkin was investigated.
Results: Endogenous Parkin is enriched in the mitochondria-associated endoplasmic reticulum membrane (MAM), preventing excessive MAM structure and calcium flux. More specifically, Parkin was found to act as a controller of IP3R-Grp75-VDAC1 complex by ubiquitinating IP3R for timely degradation, preventing calcium overflow at the MAM.
Conclusion: These results offer insights into the regulation mechanism of ER-mitochondria association and the pathogenic mechanism of Parkin deficiency in PD.
To cite this abstract in AMA style:
NJ. Xue, Y. Liu, ZH. Lin, BR. Zhang, JL. Pu. Parkin regulates ER-mitochondria association through interaction with IP3R-Grp75-VDAC1 [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/parkin-regulates-er-mitochondria-association-through-interaction-with-ip3r-grp75-vdac1/. Accessed October 5, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/parkin-regulates-er-mitochondria-association-through-interaction-with-ip3r-grp75-vdac1/