Mitochondrial DNA Regulation of the Nuclear Epigenome

Life without energy flow is impossible. Thermodynamically, an organism is a system maintained in a non-equilibrium steady state by energy expenditure, permitting it to reduce its own entropy at the expense of the environment (Morowitz, 1968; Wallace, 2010). Mitochondria are the major source of energy in the eukaryotic cell. They convert the chemical energy of ingested hydrocarbons into the high-energy bond of adenosine triphosphate (ATP). This is accomplished by the combination of electron flow through the electron transport system (ETC), the generation of an electrochemical gradient across the mitochondrial inner membrane, and the use of the resulting potential energy to generate ATP. The mitochondrial inner membrane electrochemical gradient can also be used to generate electromagnetic energy (Maxwell, 2013) and heat energy to sustain the body temperature. In order to maintain order at the expense of energy, organisms require systems to store and access information. Deoxyribonucleic acid (DNA) polymers allow information storage in the form of genes (HERSHEY and CHASE, 1952; WATSON and CRICK, 1953) which are present in the mitochondria (Attardi, 1985; M. M. NASS and S. NASS, 1963; S. NASS and M. M. NASS, 1963) and the nucleus. In the nucleus, DNA is wound around proteins called histones which in turn can be altered in structure and function by post-translational modifications (methylation, acetylation, phosphorylation, etc). In this thesis, mitochondrial energy production and genetic information storage and retrieval are discussed. The effect of mitochondrial DNA on nuclear information system is revealed and a model of how mutations in mtDNA can cause human disease is proposed