Mitochondrial genetics

Abstract

Introduction: In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders.

Sources of data: In this article, a review of the current mitochondrial genetics literature was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (www.mitomap.org), the Human DNA polymerase Gamma Mutation Database (http://tools.niehs.nih.gov/polg/) and PhyloTree.org (www.phylotree.org), a repository of global mtDNA variation.

Areas of agreement: The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases.

Areas of controversy: The exact mechanisms which govern the inheritance of mtDNA are hotly debated.

Growing points: Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease.

Keywords: genetics; mitochondria; mitochondrial DNA; mitochondrial disease; mtDNA.

Fig. 1

Mitochondrial DNA. Schematic diagram of the 16.6-kb, circular, double-stranded mtDNA molecule, where the outer circle represents the heavy strand and the inner circle the light strand. Shown are the genes encoding the mitochondrial RC: MTND1–6, MTCOI–II, MTATP6 and 8 and MTCYB; the two ribosomal RNAs (green boxes) and each of the 22 tRNAs (red spheres).

Fig. 2

Interaction between nDNA and mtDNA. Cartoon demonstrating the complex interaction between genes encoded by nDNA and the processes they control in the mitochondrion.

Fig. 3

Clinical spectrum of mitochondrial disease. Schematic diagram showing the organ and corresponding disease affected by mitochondrial dysfunction.