UQCRC1, or ubiquinol-cytochrome c reductase core protein 1, is a nuclear-encoded protein located in the inner mitochondrial membrane and is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III [1]. Mitochondrial respiratory chain is crucial for cellular metabolism, regulating processes like cell death and autophagy [7].

In Drosophila, neuronal knockdown of uqcrc1 leads to age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, which can be improved by UQCRC1 expression [1]. In mouse models, UQCRC1 p.Tyr314Ser knock-in mice exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity, and aberrant mitochondrial ultrastructures in nigral neurons, and levodopa injection can improve their motor dysfunction [3]. These in vivo studies suggest UQCRC1's role in neurodegenerative diseases, especially Parkinson's disease. However, some studies in different populations like the European and Taiwanese cohorts do not support a major role of UQCRC1 in Parkinson's disease [2,5]. In colorectal cancer, down-regulation of UQCRC1 is correlated with increased lymph node metastasis and decreased survival [4], while in pancreatic cancer, its overexpression promotes tumor growth by increasing mitochondrial oxidative phosphorylation and ATP production [6].

In conclusion, UQCRC1 is essential for mitochondrial respiratory chain function. Gene knockout or knockdown models in flies and mice have revealed its potential role in Parkinson's-like phenotypes and neurodegeneration. Additionally, its expression alterations are associated with cancer progression in colorectal and pancreatic cancers, highlighting its importance in both neurodegenerative and cancer-related biological processes.

References:

1. Hung, Yu-Chien, Huang, Kuan-Lin, Chen, Po-Lin, Lin, Chin-Hsien, Chan, Chih-Chiang. . UQCRC1 engages cytochrome c for neuronal apoptotic cell death. In Cell reports, 36, 109729. doi:10.1016/j.celrep.2021.109729. https://pubmed.ncbi.nlm.nih.gov/34551295/

2. Liao, Ting-Wei, Chao, Chih-Ying, Wu, Yih-Ru. 2022. UQCRC1 variants in early-onset and familial Parkinson's disease in a Taiwanese cohort. In Frontiers in neurology, 13, 1090406. doi:10.3389/fneur.2022.1090406. https://pubmed.ncbi.nlm.nih.gov/36570444/

3. Lin, Chin-Hsien, Tsai, Pei-I, Lin, Han-Yi, Farrer, Matthew, Wu, Ruey-Meei. . Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy. In Brain : a journal of neurology, 143, 3352-3373. doi:10.1093/brain/awaa279. https://pubmed.ncbi.nlm.nih.gov/33141179/

4. Li, Wenhua, Wubulikasimu, Gulinaizaier, Zhao, Xiaoying, Zhu, Xiaodong, Chen, Zhiyu. 2019. UQCRC1 downregulation is correlated with lymph node metastasis and poor prognosis in CRC. In European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 45, 1005-1010. doi:10.1016/j.ejso.2019.02.025. https://pubmed.ncbi.nlm.nih.gov/30842031/

5. Senkevich, Konstantin, Bandres-Ciga, Sara, Gan-Or, Ziv, Krohn, Lynne. 2020. Lack of evidence for association of UQCRC1 with Parkinson's disease in Europeans. In Neurobiology of aging, 101, 297.e1-297.e4. doi:10.1016/j.neurobiolaging.2020.10.030. https://pubmed.ncbi.nlm.nih.gov/33248804/

6. Wang, Qing, Li, Mengge, Gan, Yu, Zhang, Zhigang, Tu, Hong. 2020. Mitochondrial Protein UQCRC1 is Oncogenic and a Potential Therapeutic Target for Pancreatic Cancer. In Theranostics, 10, 2141-2157. doi:10.7150/thno.38704. https://pubmed.ncbi.nlm.nih.gov/32089737/

7. Fernandez-Mosquera, Lorena, Yambire, King Faisal, Couto, Renata, Milosevic, Ira, Raimundo, Nuno. 2019. Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis. In Autophagy, 15, 1572-1591. doi:10.1080/15548627.2019.1586256. https://pubmed.ncbi.nlm.nih.gov/30917721/