Page 16 - Q. Neuroscience

[Q. Neuroscience-9]

Intraneuronal Delivery Of Parkin Protects Neurons By

Repairing Damaged Mitochondria Through Mitophagy

Eunna Chung¹, Jiae Park¹, Wonheum Nah¹, Joonno Lee¹, Soyoung Park¹, Shinyoung Kang¹, Yunmin Park¹,
Youngsil Choi¹, Daewoong Jo¹

¹Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

Parkinson’s disease (PD) is a neurodegenerative disorder that causes abnormal movement due to the selective loss

of dopaminergic neurons in brain. Parkin is an E3 ubiquitin ligase that plays a critical role in the ubiquitination
process to fix damaged mitochondria. Improved Cell-Permeable (iCP) Parkin fused to an advanced macromolecule

transduction domain (aMTD), a recombinant protein, has been developed in E. coli system. iCP-Parkin did not
require phosphorylation of Ser-78 by PINK1 for its ubiquitination activity. In neuronal cell models, iCP-Parkin was

significantly accumulated in damaged mitochondria and ubiquitinated various substrates involved in mitophagy
(MFN1/2 and VDAC1), mitochondrial transport (Miro1/2) and mitochondrial biogenesis (PARIS). iCP-Parkin also

induced expression of mitochondrial proteins such as Cox-1, SDH-A, PGC-1α, TFAM and NRF2, which are involved
in mitochondria biogenesis. Furthermore, iCP-Parkin promoted mitophagy (~100%)/ATP level (97%), and reduced

ROS (~100%). Taken together, iCP-Parkin recovers mitochondria functionality by utilizing its ubiquitin E3 ligase
activity, and rescues neurons under PD-like pathological condition.