Back to Search
Start Over
UQCRC1 Engages Cytochrome C for Neuronal Apoptotic Cell Death
- Source :
- SSRN Electronic Journal.
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Human Ubiquinol-Cytochrome C Reductase Core Protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the disease-associated variants of UQCRC1 from patients with familial Parkinsonism, while its function remains unclear. Here we investigate the endogenous function of UQCRC1 in human neuronal cell line and Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibited age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, were ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO was also rescued by neuron-expression of UQCRC1 but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associated with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increased cytoplasmic fraction of cyt-c and activated the caspase cascade. RNAi of cyt-c or expression of the anti-apoptotic P35 ameliorated uqcrc1-mediated neurodegeneration. Our findings thus identify a novel role of UQCRC1 in regulating cyt-c-induced apoptosis.
Details
- ISSN :
- 15565068
- Database :
- OpenAIRE
- Journal :
- SSRN Electronic Journal
- Accession number :
- edsair.doi...........7f314ff965ed37d1ccfa32d933d6b2c1