Mitochondria Research Paper

Mitochondria are one of the most abundant organelles, which exercise various essential roles and function to all living things. Often time, this tremendous organelle is referred to as the powerhouse of the cell, due to their essential function in production of energy. The production of ATP, and regulation of intracellular calcium levels is also of great importance in the survival of neurons, which are cells in the brain, that make part of the Central Nervous System (CNS). Perpetual oxidative stress and damage to the Mitochondrial DNA (mtDNA), throughout aging process can causes deficiency to the metabolism energy, and ion exchange homeostasis, which result in degeneration of neurons. This mitochondrial abnormality is constantly seen in the
neurodegenerative disorder Parkinson’s disease. In recent research, this age related disease has shown great evidence to indicate that excessive oxidative stress to the mtDNA of individuals implicated with the disease is associated with trigger of apoptosis of these dopaminergic neurons. The effect of mtDNA damage is a known initiation that’s often seen in the neuron’s terminally differential cells. The mechanisms that are involved in both the damage and repair of the mtDNA are badly understood, and there are no conclusive answers. On this paper, it is hypothesized that elevated oxidative stress may be a factor of mitochondrial DNA damage in PD. It is believed that mtDNA is largely sensitive oxidative agents; due to it close immediacy with the inner mitochondrial membrane, where oxidation formation occurs, along with lack of histones protection within the membrane (1). There is sufficient evidence to show that accumulations of mtDNA play a tremendous causative role in neurodegeneration (1). Defect in mtDNA, and it greater susceptibility to mutations may cause accumulation of damaging effects caused by toxicity during reactions caused by Reactive Oxygen Species (ROS) production. The understanding of DNA repair pathways, and their causes to that leads to damaged mtDNA, will help in understanding the role that oxidative stress play in mtDNA, and it will also help in understanding the symptoms that lead to the cause of PD, which will could ultimately help in reversing PD disease. Mitochondrial DNA dysfunctions and oxidative stress can all help to study the degraded dopaminergic neurons that are seen in PD. Also, the effect of therapeutic strategies with use of animal models can also help in the understanding of this hypothesis, in suppressing the damaged mtDNA. The mitochondrion is characterized as a vital double membrane organelle, with subcellular membrane that are found in every mammalian cells.The mitochondria is greatly populated within the cytoplasm of the mammalian cell, including the exiting neuron cells. Its main function is to aid in aerobic respiration, and produce ATP via oxidative phosphorylation (OXPHOS) (1Helen). The OXPHOS is composed of over eighty distinguish polypeptides, that are all organized into five different membrane complexes. The oxidation of fats and carbohydrates, result in electrons, that are transferred to oxygen along the first four of five respiratory chain complexes, which yields water, while producing energy that is needed to pump protons across the inner membrane, starting at the matrix, and moving to the intermembrane spaces. The induction of this electrochemical gradient, facilitate the involvement of the fifth complex respiratory complex, which contains the enzyme ATP synthase, which phosphorylate ADP to form ATP. Aside from the OXPHOS metabolism, mitochondrial also, has the ability to control calcium concentration, within the cytosol, as well as regulate apoptosis. (HELEN).
Encapsulated within this complex Mitochondria organelle, is it own genome the mitochondrial DNA (mtDNA).
The mtDNA function in encoding vital subunits that are seen in the respiratory chain, where electron is able to combine with oxygen to allow the flow of energy through the mitochondria. When the mitochondrion is energized, its able to synthesize ATP, which has the ability to fuse energy dependent intracellular reactions (eg. endocytosis, ion transport, neurotransmitter biosynthesis), while sustaining vital for mitochondria. Some of these critical responsibilities include, calcium handling, ROS production as well as overall intracellular signaling. The mtDNA is also incapable of transmitting through the nuclear DNA (nDNA). In both human and various multicellular organism, the mtDNA, is inherited from the mother’s ovum exclusively, which mean that the mitochondria inheritance non-Mendelian. Quite interestingly, the mtDNA codes for eight percent of the mitochondrial RNA. In humans and animals, the mtDNA, is capable of forming moles that are closed circular, which contains approximately, 16,569 DNA base pairs. Each of these molecules, tend to include a complete set of mitochondrial gene. The mitochondrion, contains roughly, 3000 various types of protein. However, it seen that only 13 of these protein are coded within the mtDN. Any mutation that is induced in the mtDNA, will manifest into function problems. Slight alteration with any of the various enzymes that are associated
with the mtDNA. Chromosomal mutations that are seen with the mtDNA, causes specific alterations to tissues, due to their needs for high energy needs, along with both catabolism and anabolism of specific neurotransmitter. These identification of mutation, that are seen in the mtDNA, suggest that the neuron cells is especially sensitive to mitochondrial dysfunctions (1). Also, compared to any other cell types, neurons display a great amount of hypersensitivity to mitochondrial toxins. These alterations are seen greatly in PD.
In order to understand how oxidative stress contributes to the alterations that are seen in the mtDNA of PD there has to be understanding of the mechanism that leads to the DNA damage, and ways of repairing to degrade these oxidative stressors.
The mechanism for this is still poorly understood, and misleading as recent researches has shown (1). The DNA reliability is crucial the role in the normal cell growth and damage to the mitochondrial DNA can cause serious consequences. DNA damage can be caused by both endogenous, as seen in ROS, and exogenous due to environmental causes shch as ionizing radiation, and pesticides as sppen in 80% of sporadic PD. DNA modification tend to involve key types. The first type being principal being, the apyrimidic site, which cause the loss of a base, as a result of N-glycosil bond cleavage. Next, Deamination, which causes the loss of specific amino
group.