Patient-derived lymphoblastoid cell lines harboring mitochondrial DNA mutations as tool for small molecule drug discovery

BMC Res Notes. 2018 Mar 27;11(1):205. doi: 10.1186/s13104-018-3297-6.


Objective: Mitochondrial diseases are a group of devastating disorders for which there is no transformative cure. The majority of therapies for mitochondrial disease-approved, previously tested, or currently in development-are small molecules. The implementation of better cell-based models of mitochondrial disease can accelerate and improve the accuracy of small molecule drug discovery. The objective of this study is to evaluate the use of patient-derived lymphoblastoid cell lines for small molecule research in mitochondrial disease.

Results: Five lymphoblastoid cell lines derived from mitochondrial disease patients harboring point mutations in mtND1, mtND4, or mtATP6 were characterized in two high throughput assays assessing mitochondrial function. In a pilot "clinical trial in a dish" experiment, the efficacy of idebenone-an approved therapy for mitochondrial disease-on the lymphoblastoid cell lines was tested. Idebenone increased the basal respiration of all lymphoblastoid cell lines except those harboring the 8993T>G point mutation in mtATP6. Our results posit lymphoblastoid cell lines as a strong model for mitochondrial disease research with small molecules and have implications for the clinical efficacy of idebenone.

Keywords: ATP6; High-throughput screening; Idebenone; Lymphoblastoid cell lines; Mitochondria; Mitochondrial disease; ND1; ND4; Respiration.

MeSH terms

  • Adult
  • Cell Line
  • Child
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Drug Discovery / methods*
  • Female
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Oxygen Consumption / drug effects
  • Point Mutation*
  • Small Molecule Libraries / therapeutic use
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / therapeutic use
  • Young Adult


  • DNA, Mitochondrial
  • Small Molecule Libraries
  • Ubiquinone
  • idebenone