mitochondria AND THE ORIGIN OF LIFE
Mitochondria are double-membrane bound cellular organelles found in all cells, except red blood cells. Cells can contains 100s to thousands of mitochondria. Mitochondria contain their own DNA genome known as mitochondrial DNA (MtDNA) which is separate from the nuclear genome. It is believed that mitochondria originated about 2 billion years ago when an aerobic bacterium invaded the primitive eukaryotic cell. Through reductive evolution, the majoity of genes were transfered from the eubacterial genome to the nucleus of the host, however a small DNA genome remained within the mitochondrial organelle.
“It seems that all eukaryotic cells either have, or once had (and then lost) mitochondria. In other words, possession of mitochondria is a sine qua non of the eukaryotic condition”
― Nick Lane, Power, Sex, Suicide: Mitochondria and the Meaning of Life
WHAT DO MITOCHONDRIA DO?
Mitochondria are often described as the ‘powerhouses of the cell’ since they produce the majority of cellular energy via oxidative phosphorylation (OXPHOS), a process involving the transfer of electrons along a series of protein complexes in the inner mitochondrial membrane. The process of electron transport results in the production of some reactive oxygen species (ROS) which play an important role in normal intracellular signalling pathways. In addition to cellular energy production, mitochondria play many other roles in the cell including homeostasis of cellular calcium, formation of iron-sulphur clusters and regulation of the intrinsic apoptosis pathway. Given their importance in maintaining normal cellular function, it is perhaps no surprise that mitochondria have become a focus of increased attention in terms of their potiential impact on the pathogenic mechanisms of human disease.
In addition to the DNA found in the cell nucleus, we also have DNA within our mitochondria. This mitochondrial DNA is a small, circular genome of 16,569 base pairs encoding genes vital to the energy production process. Each mitochondrion has multiple copies of mitochondrial DNA, MtDNA can be present in 100s to thousands to copies per cell in the body depending on the bioenergetic requirements of the host cell. MtDNA encodes subunits of the electron transport chain and therefore is required to produce cellular energy in the form of ATP. However MtDNA can also act as an inflammatory molecule since it resembles bacterial DNA, resulting in activation of pathways leading to enhanced cytokine production and chronic inflammation
MITOCHONDRIA AND DISEASE
With only 13 proteins encoded by mtDNA, the mitochondrion is under dual control relying on many other proteins encoded by the nuclear genome to function normally. Mutations in these genes can lead to mitochondrial dysfunction, manifesting at a cellular level in various ways, including OXPHOS deficiency, reduced mtDNA copy number or disruption of the mitochondrial network. The clinical symptoms associated with mitochondrial dysfunction fall under the umbrella term of ‘mitochondrial disease’, which encompasess a clinically and genetically diverse group of conditions with systemic effects on the body’s cell and organs.These are broadly categorised as either primary or secondary mitochondrial disease, however there is some overlap regarding the definition of these two main groups. In addition, mitochondrial dysfunction has been postulated to play a key role in many other common disease, which were not traditionally throught to be mitochondrial disease. These include cardiovascular and neurodegenerative disease as well as diabetic complications.