Environmental Modifiers of Mitochondrial Disorders

Abstract

The influence of epigenetic environmental factors on the course of heritable mitochondrial disorders has long been known to the researchers in the field. For example, in a study of a large group of affected and unaffected carriers of the three primary mitochondrial DNA point mutations (m.3460G>A, m.11778G>A, and m.14484T>C) causing Leber’s Hereditary Optic Neuropathy (LHON), Kirkman et al. [3] identified that tobacco use and heavy consumption of alcohol are not only strong risk factors for loss of vision in LHON but also are responsible for the marked incomplete penetrance observed in this primarily mitochondrial disease [3]. This finding is important as it has a direct disease preventive implication for the asymptomatic carriers of LHON mutation. LHON is predominantly a male disorder as about 80% of the affected patients are male and, in many affected pedigrees, disease penetrance is much higher (50%) in males harboring the mutation than that in female (10%) carriers [4]. Currently, the cause of this gender difference remains unknown. However, a recent study in a LHON cybrid cell model has provided strong evidence that estrogen might have a protective role against the damaging effects of LHON mutations, and that could explain the lower penetrance of the disease observed in female mutation carriers [5].