Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To illustrate the mechanism of CHCHD2 in regulating MICOS and mitophagy in Parkinson’s disease.To illustrate the mechanism of CHCHD2 in regulating MICOS and mitophagy in Parkinson’s disease.
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitophagy, the selective form of macro-autophagy, plays an important role in mitochondrial quality control and is involved in pathology of PD. Recently, coiled-coil helix coiled coil helix domain containing 2 (CHCHD2) was identified associated with autosomal dominant Parkinson’s disease (PD). However, the mechanism of CHCHD2 in mitophagy in PD remains unclear.
Method: Mitochondria were isolated with a Mitochondria Isolation Kit. Mitochondrial morphology changes were measured via live cell imaging. ATP level was assessed by using a Luminescent ATP Detection Assay Kit. PINK1-GFP or Parkin-GFP plasmid was transfected into HeLa cells stably expression CHCHD2-flag or control vector and treated with or without MPP+ to address the mechanism of CHCHD2 in regulation of mitophagy. The interaction of CHCHD2 with the MICOS was performed by immunofluorescence and co-immunoprecipitation (Co-IP) assays. The role of CHCHD2 in stability of MICOS was assessed by using blue native electrophoresis.Adeno-associated viral vectors (GV411/AAV9) expressing 3Flag-tagged human CHCHD2 and vector were delivered to the substantia nigra pars compacta (SNpc) of mice by unilateral stereotactic injection to explore the effects of CHCHD2 in MPTP -induced mice model of PD.
Results: CHCHD2 can protect mitochondrial morphology and function in a MPP+-induced cell model. CHCHD2 suppressed MPP+-induced overactivation of mitophagy. CHCHD2 inhibited MPP+ induced aggregation of Parkin on mitochondria. CHCHD2 suppressed MPP+-induced translocation of PINK1 to the mitochondria. CHCHD2 can interact with MICOS. CHCHD2 maintained MICOS and protected against MPP+-induced MICOS impariment. CHCHD2 can protect dopaminergic neurons in an MPTP induced mouse model of PD.
Conclusion: We highlighted that CHCHD2 can inhibit PINK1/Pakrin mediated mitophagy in an experimental model of PD. CHCHD2 interacted with Mic10 and MICOS, which may related to the regulation of PINK1 relocation in mitophagy. However, further studies are needed to clarify the mechanisms among CHCHD2, Mic10, CHCHD10 and PINK1.
To cite this abstract in AMA style:
X. Chen, M. Zhou, XQ. Zhu, SX. Huang, WY. Guo, Z. Pei, PY. Xu. CHCHD2 maintains the MICOS and inhibits PINK1/Parkin mediated mitophagy in an experimental model of Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/chchd2-maintains-the-micos-and-inhibits-pink1-parkin-mediated-mitophagy-in-an-experimental-model-of-parkinsons-disease/. Accessed May 11, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/chchd2-maintains-the-micos-and-inhibits-pink1-parkin-mediated-mitophagy-in-an-experimental-model-of-parkinsons-disease/