Mitochondrion (Creative Image)
and in our environment.
Years ago, the Eukaryotic cell developed as a symbiotic relationship between a prokaryotic cell and a proteobacteria. The prokaryotic cell may have been an archaea. The proteobacteria was was incorporated into the cell as an endosymbiont. As gene transfer took place between mitochondrial DNA and the cell's nuclear DNA, the extent of the mitochondrial DNA (mtDNA) decreased and the nuclear DNA incorporated more of the functions performed previously by mitochondrial DNA. As this occured, the relationship changed from being symbiotic to the development of the mitochondrion as an organelle within the cell.
Much of the work developing the theory of symbiogenesis was done by Lynn Margulis in a 1967 paper.. The theory behind symbiogenesis is a very important topic with wide ranging implications due to the complexities involved in the interoperablity of nuclear DNA and mitochondrial DNA. These issues are ongoing and represent a major challenge in understanding a wide range of scientific issues confronting our society today.
Mitochondria are present in most living cells that include DNA. Mitochondria are responsible for a large portion of the energy generated by the cell. Mitochondria are responsible for the generation of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) through aerobic processes using its electron transport chain (ETC). The energy generated as ATP is many times greater than the energy generated through anaerboic glycolysis, which is an energy generation process that does not use oxygen.
The use by the cell of anaerobic vs aerobic respiration has significance in studying various physiological processes which occur throughout the body. These issues have implications in wide ranging areas from cancer to the relationship between sleep and wakefulness.
As energy is generated throughout the body, principles of conservation of energy must be satisfied. Whether energy is generated through aerobic respiration and Oxidative Phosphoylation (OXPHOS) using the mitochondrial electron transport chain (ETC), energy generation requires inputs and outputs that must be balanced. This is a principle called "conservation of energy". OXPHOS generates ATP, the "energy equivalent of currency" in the body, energy in the form of heat, and outputs such as oxygen radicals (Reactive Oxygen Species (ROS)) as a byproduct of the process.
Oxygen Canisters
Oxygen reactive species such as superoxide (O-), hydrogen peroxide (H202) and the hydroxyl radical (OH-) can be generated depending upon a number of factors. This includes natural process in the body involving signaling and homeostasis and also exposure to a number of environmental factors which may increase their generation. Antioxidants may help the cell counter some of the impacts of reactive species.
Exposure to pollution, chemicals, toxins and radiation may increase oxygen reactive species exposure. Radiation exposure may include ionizing radiation or non-ionizing radiation such as cosmic rays (e.g. gamma rays ). Geomagnetic storms and reduced ozone layer protection at polar regions as Antarctica and the Arctic may increase such exposure, with greater historical ozone depletion over the Antarctic.
I photographed in Antarctica in November/December 2004, and in October 2006 and photographed in the Arctic in July 2005. The year 2006 saw the worst levels of depletion (2004 Image-Halley Bay Station, Antarctica) in recorded history.
Cellular processes guide apoptosis, or programmed cell death under a number of circumstances, generating an intrinsic pathway or extrinsic pathway for cell death. Reactive species play key roles in this process, as signaling mechanisms, and also in promoting cell death, as free radicals generated by a variety of situations trigger apoptosis.
Mitochondria play a large role in enforcing 'group identity' in a cell. The mitochondria helps to sustain certain energy needs within the body and when certain system parameters (group identity system requirements) are not fulfilled, the process of apoptosis or programmed cell death is intended to kill off certain cells that do not meet those system parameters.
Mitochondria can be loosely or tightly coupled; this means that they can "leak" protons so that more heat is produced (uncoupled) relative to amount of ATP produced; there are certain uncoupling proteins that aid in this process, which decreases the generation of potentially damaging oxygen radicals. A highly coupled system will thus be more efficient in the generation of energy, less efficient in generating heat, and will generate more oxygen radicals, which can cause damage to the system. A more loosely coupled system will produce more heat, will generate less oxygen radicals, and will be less efficient in generating energy. A loosely coupled system will be more valuable in colder climates due to the greater heat protection. A tightly coupled one will result in more conditions, such as diabetes, which are impacted by the generation of oxygen reactive species.
The generation of reactive oxygen species is a significant issue in DNA damage and mutations involving mutagenesis. Mitochondrial DNA (mtDNA) are much less protected from the generation of reactive species than nuclear DNA. In the proverbial sense, they sit at the edge of the oxidative phosphorylation 'fiery furnace' and absorb more damage than nuclear DNA. Nuclear DNA has greater protection from reactive species, being protected by histones and telomeres.
Mitochondria can be damaged by reactive species, however, there is a certain amount of punishment that mitochondria can take before a process called heteroplasmy takes place. Heteroplasmy in the mitochondria is a process where, due to mutation, mitochondrial damage or other process, more than one mitochondrial genome can exist. This process may be associated with mitochondrial disease and be more extensive the greater the degree of heteroplasmy. However some individuals may live to long ages with some degree of heteroplasmy.
There is a basic problem with mitochondrial damage and mutation in so far as the mtDNA and the nuclear DNA interoperate in the OXPHOS process. This is because, as mentioned earlier in the article, some mitochondrial functions ages ago were shifted into the nuclear DNA through the process of gene transfer. Cytochrome C belongs to the cytochrome c family of proteins and is an integral part of the ETC. Cytochrome C has a long history, which goes back to time periods when the Earth was subject to heavy amounts of radiation. Illnesses associated with Cytochrome C may involve both nuclear DNA and mitochondrial DNA.
Since Nuclear DNA has greater protection than mitochondrial DNA (mtDNA) from the insult of reactive species, the degree of damage in each case will differ, or in the case of nuclear DNA, there may be minimal or no damage. This will lead to interoperability issues as mutations and damage occurs. Interoperability is the ability of systems to work together. As oxidative stress occurs at different rates and to different but inter-operating parts of the cell (mtDNA and nuclear DNA), illness and damage occurs, and potentially mutations. This occurs in systems requiring heavier use of energy, including muscles. Respiratory muscles bear the burden of oxidative stress, as these muscles are those subject to the greatest use during sleep. Sleep apnea may be associated with higher levels of exposure to oxidative stress.
As we are subject to greater and greater levels of substances that create oxygen reactive species, we can see that problems can add up. There are greater and greater chances of damage and mutations, the probability of heteroplasmy increases, the levels of heteroplasmy in the cell may come closer to the levels of heteroplasmy that may be tolerated in the cell without incurring mitochondrial disease.
We can see, therefore, that exposure to reactive species such as environmental toxins and radiation may provide for mutations in both nuclear and mitochondrial DNA, that these processes may occur at different rates, and that past a certain point, mitochondrial disorders may develop as the result of such exposure. At the same time, mutations that are beneficial may sometimes occur, and mutations and damage that are harmful may indeed result. The ability for mutations that are adaptive to occur may reflect the ability of the mitochondrial DNA and the nuclear DNA to inter-operate, which is statistically difficult, considering the conditions under which each of these processes work.
Thus any process which seeks to advance a species by introducing mutagenic factors via the use of the creation of oxygen radicals must take into consideration that mutations and damage may result in the process and that individuals may be harmed in such process. Due consideration must exist for who is subject to such exposure, and when the risk of subjecting certain individuals to such exposure constitutes a material risk that makes such experimentation untenable in a civilized society.
The risks of exposure to reactive species increases with the degree and length of the exposure, impacting the risk of early morbidity and mortality. Mutagenesis is more effective when it occurs in germ line cells which can pass mutations, either favorable, or unfavorable on to the next generation
Where such experiments are conducted, they must be conducted in an ethical fashion, they must be done with full informed consent of those involved, they must adhere to the law of civilized nations, and the ongoing experience of such studies must be monitored and measured so that those involved are not unduly harmed and the patient population put at excessive risk.
It must be made abundantly clear that if our society depends upon mutations to adapt the species to future environmental (or other) challenges, that those who have been subject to environmental (or other) assaults for such purpose be treated with due respect, that their contributions be valued, and their condition be measured, monitored and treated. It is clear that what these individuals are doing on a collective basis is aiding the future development of humanity. They are test subjects in a process that will benefit others, later.
What are our future ecological and planetary challenges and how can we adapt to them? How do these challenges impact our exposure to environment risks and how we deal with them? These are all important issues.
The mitochondria, as a vital cog in the production of energy has a very important part of the story that must be told as we seek to deal with the environment, climate change and other planetary challenges that we face.
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