@article{071949b430274643bb1b3dbedd52423f,
title = "Cross talk between SOD1 and the mitochondrial UPR in cancer and neurodegeneration",
abstract = "The mitochondrial unfolded protein response (UPRmt)is rapidly gaining attention. While the CHOP (ATF4/5)axis of the UPRmt was the first to be described, other axes have subsequently been reported. Validation of this complex pathway in C. elegans has been extensively studied. However, validation of the UPRmt in mouse models of disease known to implicate mitochondrial reprogramming or dysfunction, such as cancer and neurodegeneration, respectively, is only beginning to emerge. This review summarizes recent findings and highlights the major role of the superoxide dismutase SOD1 in the communication between the mitochondria and the nucleus in these settings. While SOD1 has mostly been studied in the context of familial amyotrophic lateral sclerosis (fALS), recent studies suggest that SOD1 may be a potentially important mediator of the UPRmt and converge to emphasize an increasingly vital role of SOD1 as a therapeutic target in cancer.",
keywords = "ALS, Cancer, Estrogen receptor, Mitochondria, Neurodegeneration, ROS, SIRT3, SOD1, SOD2, UPR",
author = "Maria Gomez and Doris Germain",
note = "Funding Information: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal, neurodegenerative disease characterized by damage of motor neurons of the spinal cord, which leads to paralysis. While sporadic cases of no known etiology account for the majority of ALS cases, mutations in SOD1 are responsible for approximately 20% of familial ALS (fALS) ( Rosen et al., 1993 ; Andersen, 2006 ). More than 180 different causative mutations in the SOD1 gene have been identified in fALS patients ( Keskin et al., 2016 ). It is widely accepted that SOD1-linked fALS is partly caused by a toxic gain-of-function of the SOD1 mutant rather than loss of function ( Andersen, 2006 ). This interpretation is supported by the fact SOD1 mutants without enzymatic activity also cause ALS ( Agar and Durham, 2003 ). Funding Information: We would like to thank all members of the Germain lab. This study was supported by the NIH R01CA172046 to D.G, NIH R01NS084486 award to D. G and G. M and the NIH supplement to M.G. The core facilities used in this study are supported by P30 grant CA196521. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jul,
doi = "10.1016/j.mcn.2019.04.003",
language = "English",
volume = "98",
pages = "12--18",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",
}