| Outline of Final Research Achievements |
We recently identified CHCHD2 mutations as a novel gene associated with autosomal dominant Parkinson’s disease (PD). CHCHD2 is localized to mitochondria and linked to mitochondrial complex IV function, however, its pathogenic mechanisms remain largely unknown. To elucidate the involvement between CHCHD2 and mitochondria, we generated CHCHD2-KO cells using CRISPR/Cas9 techniques, and performed mitochondrial phenotyping. Steady state ATP level and ATP synthesis rate were dramatically decreased in CHCHD2-KO cells. Steady state ATP level was partially rescued by overexpression of wildtype CHCHD2, but not by PD linked mutants of CHCHD2 (T61I and R145Q). Mitochondrial membrane potential, ROS, and superoxide were markedly and significantly increased in CHCHD2-KO cells. In conclusion, Loss of CHCHD2 impairs multiple mitochondrial functions and CHCHD2 KO cells may provide a useful cell model for understanding CHCHD2 function and pathophysiology of CHCHD2 mutations and PD.
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