Cytoplasmic hybrid (cybrid) cell lines as a practical model for mitochondriopathies

• The cytoplasmic hybrid (cybrid) model can be used to determine mitochondrial DNA (mtDNA) contributions to phenotypic alterations.
• Cybrids are used to study mitochondriopathies such as Parkinson’s disease and Alzheimer’s disease.
• mtDNA heteroplasmy threshold and nuclear DNA-mtDNA compatibility can be determined using cybrid models.

Cytoplasmic hybrid (cybrid) cell lines can incorporate human subject mitochondria and perpetuate its mitochondrial DNA (mtDNA)-encoded components. Since the nuclear background of different cybrid lines can be kept constant, this technique allows investigators to study the influence of mtDNA on cell function. Prior use of cybrids has elucidated the contribution of mtDNA to a variety of biochemical parameters, including electron transport chain activities, bioenergetic fluxes, and free radical production. While the interpretation of data generated from cybrid cell lines has technical limitations, cybrids have contributed valuable insight into the relationship between mtDNA and phenotype alterations. This review discusses the creation of the cybrid technique and subsequent data obtained from cybrid applications.

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