Mitochondrial DNA mutation m.3243A>G is associated with altered mitochondrial function in peripheral blood mononuclear cells, with heteroplasmy levels and with clinical phenotypes

摘要

Aims To investigate the associations among heteroplasmy levels (i.e. the proportions of mutant and wild-type mitochondrial DNA in the same cell), mitochondrial function and clinical severity of the m.3243A>G mutation. Methods A total of 17 participants carrying the m.3243A>G mutation and 17 sex- and age-matched healthy controls were included in this study. Heteroplasmy levels of the m.3243A>G mutation in leukocytes, saliva and urine sediment were determined by pyrosequencing. The clinical evaluation included endocrinological, audiological and ophthalmological examinations. Mitochondrial function was determined in peripheral blood mononuclear cells isolated from participants. Results Heteroplasmy levels in urine sediment were higher than those in leukocytes and saliva. Reduced levels of adenosine triphosphate and mitochondrial membrane potential, and increased reactive oxygen species production were observed in mutant peripheral blood mononuclear cells (all P G mutation.