Transcriptome analysis in mitochondrial disorders

The spectrum of genetic disorders associated with primary mitochondrial dysfunction ranges from isolated hearing loss to lethal neonatal syndromes. Mitochondrial biogenesis and function relies on the enigmatic interplay of the mitochondrial and nuclear genome and allows for adjustment of energy consumption to substrate availability and adaption to genetic and toxic stressors. Whole transcriptome studies permit a global perspective on these events and promise deeper insight into mitochondrial physiology and dysfunction. Data coming from microarray studies has revealed the activation of an intricate signaling network that promotes bioenergetic adaption through autophagy and enhanced mitochondrial biogenesis. The effectors of this network are currently under much investigation for their therapeutic potential. Microarray data also implicate a profound impact of mitochondrial dysfunction on global nuclear transcription activity through alteration of genomic stability, cell cycle progression and epigenetic regulation. In this review, results of gene expression studies performed on human and animal tissue as well as cell culture models with mitochondrial dysfunction are summarized and discussed.

► We explain the basic principles of genetic transmission of mitochondrial disorders as well as their multifactorial nature. ► We describe the basic principles of mitochondrial biogenesis, its genetic disruption and endogenous compensatory mechanisms. ► We provide an overview of gene expression studies in this field and discuss the results and conclusions in relation to established and novel disease concepts. ► We provide a prospect of potential therapeutic implications coming from this data.