CHCHD2 deficiency leads to mitochondrial dysfunction in human neuroblastoma SY-SY5Y cells Taku Amo1, Manabu Funayama2,3,4, Jin Sung Park5, Norihiko Furuya6, Shinji Saiki3, Wado Akamatsu4, Carolyn M Sue5, Nobutaka Hattori2,3,4 1Department of Applied Chemistry, National Defense Academy, Yokosuka, Japan; 2Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan; 3Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; 4Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Tokyo, Japan; 5Department of Neurogenetics, Kolling Institute, Royal North Shore Hospital, St. Leonards, New South Wales, Australia; 6Department of Research and Therapeutics for Movement Disorders, Graduate School of Medicine, Juntendo University, Tokyo, Japan
We recently identified coiled-coil helix coiled-coil helix domain containing 2 (CHCHD2) mutations as a novel gene associated with autosomal dominant Parkinson's disease. CHCHD2 is localized to mitochondria and linked to mitochondrial complex IV function, however, pathogenic mechanisms remain largely unknown. To elucidate the involvement between CHCHD2 and mitochondria, we generated CHCHD2 knockout SH-SY5Y neuroblastoma (CHCHD2-KO) cells using CRISPR/Cas9 technology. CHCHD2-KO cells showed growth retardation in glucose-free media instead supplemented with galactose, indicating mitochondrial oxidative phosphorylation deficiencies. Complex IV activity was significantly decreased in CHCHD2-KO cells. These results suggested loss of CHCHD2 impairs mitochondrial oxidative phosphorylation and CHCHD2 KO cells may provide a useful cell model for understanding CHCHD2 function and pathophysiology of CHCHD2 mutations in Parkinson's disease.