Mitochondria in Health and Disease

To be published June 2017
Prof. Zofia Chrzanowska-Lightowlers
Wellcome Trust Centre for Mitochondrial Research, Newcastle, UK

Mitochondria are increasingly being recognised as organelles that contribute far more to cell metabolism than just the efficient generation of ATP. Other functions include roles in calcium metabolism, apoptosis, haem biosynthesis, and iron-sulphur cluster formation. Characterisation of mitochondrial dysfunction is also the subject of much research as it causes a... read morewide range of diseases.
Mitochondria are unusual in that they have their own genome, mtDNA, which is distinct from the nucleus. This genome is exclusively maternally inherited in humans and encodes 37 genes that are not represented in the chromosomal DNA. Mitochondrial DNA is present in multiple copies per cell, and when mutations arise they are not necessarily present in all the mtDNA copies within the cell. Such a mixed population is described as heteroplasmy. This phenomenon creates a substantial problem when giving genetic counselling to those considering having a family as it is not possible to predict with absolute certainty how much, or if any, of the mutated mtDNA will be inherited by the children. Enormous strides have been made in what can be offered during pregnancy (reproductive options include genetic counselling, ovum donation, antenatal diagnosis (by CVS biopsy) and pre-implantation genetic diagnosis (PGD)). Very recent legislation now means that research is permitted to test the possibility of IVF techniques to prevent the transmission of the mutated mtDNA.
Although many mutations in mtDNA have been identified in patients suffering from mitochondrial disease, technological advances now mean that patients suffering from these diseases can have both their mitochondrial and nuclear genome sequenced to identify which gene harbours the causative mutation. As a consequence of this wider genome analysis more proteins involved in mitochondrial homeostasis have been identified and further characterisation of their specific functions are ongoing.
Furthermore, with demographics indicating an increase in the ageing population and the consequent burden on health resources, it is important that we understand the contribution that mitochondria play in ageing as well as disease. To do this effectively we need to better understand the regulation of the various ongoing processes in healthy mitochondria.