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Generation of Leigh Syndrome Cell Models
Author(s) -
Alvarado Joshua
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb209
Subject(s) - respiratory chain , mitochondrial disease , mitochondrion , reactive oxygen species , mitochondrial respiratory chain , rotenone , electron transport chain , disease , leigh disease , cell , mutation , mitochondrial dna , bioinformatics , chemistry , microbiology and biotechnology , biology , medicine , genetics , biochemistry , gene
Leigh Syndrome (LS) is a neurological disease that stems from mutations in the subunits of mitochondrial respiratory chain subunits. These mutations decrease electron transport chain (ETC) efficiency, leading to decreased cellular ATP levels and increased reactive oxygen species (ROS) levels. There is currently no therapeutic approach to combat this degenerative disorder, and patients typically die by 8–10 years of age. There are also very few models with which to study this disease. We have generated LS cell models using both a chemical and genetic approach. Chemically, we inhibit ETC activity with low levels of rotenone, an ETC poison, in order to suppress ETC‐dependent ATP generation to levels seen in LS patients. Genetically, we use siRNA to knock down the ETC subunits that are mutationally inactivated in LS patients, also disrupting ETC function. Through these approaches, we have constructed LS cell models that can now be used to investigate potential therapeutics. Support or Funding Information CSUPERB New Investigative Grant