The mitochondrion is an organelle found in the body cells responsible for energy production through respiration in body cells. Additionally, it also takes part in other activities such as cellular differentiation, signaling, and control of cell cycle and growth. The number of these organelles in a cell depends on the energy requirements and functions of the particular cell [O'rourke, 2013]. For instance, while liver cells have over two thousand mitochondria, the red blood cells have none. It is divided into several compartments with each having specialized functions. According to O'rourke , the mitochondria have their own genome despite the fact that the DNA material of cells is stored in the nucleus. The normal process of maintaining homeostasis of the mitochondrial physiology has been linked to several disorders such as mitochondrial myopathy. This disease affects the muscle tissues due to inadequate production of energy in the cells as a result of abnormal functioning of the mitochondria.
Role of Mitochondria in Organism
The normal activities associated with the mitochondria involve the production of ATP by phosphorylating ADP and regulating cellular metabolism. A large number of proteins present in the inner membrane of the organelle are responsible for energy conversion. Break down of glucose in the cytosol leads to the formation of NADH and pyruvate through aerobic respiration. In the limited presence of oxygen, like in strenuous exercises, anaerobic respiration occurs to break down the glycolytic products but is independent of the mitochondria [Li, White, Warren, and Wohlgemuth, 2016]. However, according to Romanello and Sandri , ATP production in the mitochondria is over ten times higher in aerobic respiration as compared to fermentation. Also, research studies have indicated that the mitochondria are capable of producing high amounts of ATP in the absence of oxygen by using another substrate such as nitrite [Agrawal and Mabalirajan, 2016]. When the energy is produced, in the form of ATP, it passes out through the inner membrane using specific proteins and across the outer membrane using porins. ADP uses the same route to travel back to the organelle for phosphorylation.
The process of energy conversion is aided by the pyruvate and citric acid cycle. The process of Glycolysis produces pyruvate molecules that are transported actively into the mitochondrial matrix. In the matrix, these molecules can either undergo carboxylation into oxaloacetate or oxidation to form NADH, carbon dioxide, and acetyl-CoA [O'rourke, 2013]. The oxaloacetate produced replenishes the amount in the citric acid cycle which increases its capacity to metabolize acetyl-CoA to produce more energy [Franzini-Armstrong, 2014]. During the cycle, all the intermediates undergo regeneration at each stage. Therefore, the addition of a substrate such as an oxaloacetate to the cycle produces an anaplerotic effect while removal leads to a cataplerotic effect [Romanello and Sandri, 2016]. Therefore such processes dictate the amount of oxaloacetate required for the production of citric acid. Consequently, it regulates the amount of ATP energy produced in the cell. In some cases such as the increased activity of the muscle tissues, an increased rate of metabolism is required to avoid myopathy. On the other hand, acetyl-CoA can be derived from beta-oxidation of fatty acids or pyruvate oxidation and is the only substrate that enters the cycle repeatedly. One molecule of acetyl-CoA gets used in each cycle for every oxaloacetate molecule present in the mitochondrial matrix and cannot be regenerated [O'rourke, 2013]. The acetate portion of the acetyl-CoA is oxidized to produce water and carbon IV oxide while the energy produced in this reaction is utilized in the form of ATP.
In the liver, pyruvate present in the cytosol of the cells undergoes carboxylation into oxaloacetate. This process occurs along the gluconeogenic pathway responsible for deaminated alanine and lactate into glucose through the stimulation by adrenaline and glucagon in the blood. In this case, the addition of oxaloacetate is not anaplerotic because malate, another intermediate of the cycle, is removed from the mitochondria and converted to oxaloacetate in the cytosol [Agrawal and Mabalirajan, 2016]. This process occurs as a reverse of glycolysis as the substrate is finally converted into glucose. According to Li et al. , during the oxidation of acetyl-CoA in the citric acid cycle, one molecule of FADH2 and three molecules of NADH are produced. These cofactors become the source of electrons for converting GTP molecules into ATP and for the electron transport chain.
The electron transport chain aids in the transfer of redox energy from FADH2 and NADH to oxygen. Apart from the citric acid cycle, these molecules are also produced through glycolysis in the cytoplasm. The malate-aspartate shuttle and the glycerol phosphate shuttle aids in importing the reducing equivalents from the cell cytoplasm [Franzini-Armstrong, 2014]. The transfer is performed by the protein complexes such as cytochrome C reductase, NADH dehydrogenase, and cytochrome C oxidase present in the inner membrane [Agrawal and Mabalirajan, 2016]. As a result, the energy released is used for pumping protons into the intermembrane space. Although this process is efficient, Li et al.  indicate that some few electrons may reduce oxygen prematurely and result in the formation of reactive oxygen species such as superoxide. It causes oxidative stress to the mitochondria and may result in reduced function attributed to the aging of the organelle. With an increased concentration of protons in the intermembranous space, the inner membrane has a strong electrochemical gradient. Therefore, the ATP synthase complex can aid in returning protons to the matrix where its potential energy is utilized for synthesizing ATP from inorganic phosphate and ADP through chemiosmosis.
In some instances, protons may find their way into the matrix of the mitochondria without being involved in the synthesis of ATP. The process, also known as mitochondrial uncoupling or proton leak, occurs through facilitated diffusion [O'rourke, 2013]. It is utilized in the production of heat energy in the body given that there is unharnessed potential energy in the electrochemical gradient of the proton. Thermogenin is a proton channel that facilitates this process. It is found in the brown adipose tissues present at the birth of human beings for generating heat of the body.
How Mitochondria Relate to The Storage of Calcium Ions?
Another function associated with mitochondria in maintaining homeostasis is the storage of calcium ions. The presence of free calcium in the cell is responsible for the regulation of various physiologic functions and helps in transducing signals in the cells [Franzini-Armstrong, 2014]. Therefore, mitochondria act as a cytosolic buffer of calcium in the cell, which contributes to maintaining normal levels. The organelles work together with the endoplasmic reticulum in regards to the storage of calcium ions. The mitochondrial calcium uniporter located in the inner membrane takes up calcium into the matrix using the membrane potential of the mitochondrion. These ions can then be released back into the cytosol using the calcium-induced calcium-release or the sodium-calcium exchange protein pathways [Agrawal and Mabalirajan, 2016]. In some cases, this process may initiate calcium waves or spikes that cause a change in the membrane potential. As a result, the second messenger system may be activated and cause the release of neurotransmitters from nerve cells and hormones from endocrine cells. The influx of calcium ions into the mitochondria has also been implicated in the regulation of respiratory bioenergetics which may reduce oxidative stress [Li et al., 2016]. According to O'rourke , in neurons, further increases in the number of calcium ions in the cytosol or mitochondrial matrix helps in synchronizing the mitochondrial energy metabolism with the neuronal activity.
The mitochondria-associated ER membrane (MAM) also plays a critical role in the physiology and homeostasis of the mitochondria. This structure found in the outer membrane of the mitochondria has been found to contain enzymes used in phospholipid exchange as well as calcium signaling channels [Agrawal and Mabalirajan, 2016]. These enzymes include phosphatidylserine decarboxylase and phosphatidylserine synthase and are used in the biosynthesis of lipids. The mitochondria is therefore involved in the transport of products and intermediates products of phospholipid biosynthetic pathway across organelles and anabolism of glycosphingolipids [Romanello and Sandri, 2016]. The MAM allows lipid transfer between layers with little use of ATP. Additionally, the MAM may also play a role in the secretory pathway in which it acts as an intermediate destination between the Golgi and the rough endoplasmic reticulum during the assembly and secretion of VLDLs [Li et al., 2016].
The energy produced in the cell in the form of ATP is crucial at the cellular level and as well as the tissue and organs. In addition to cellular metabolism, ATP produced extracellularly, together with adenosine produced as a result after breakdown is involved in several biological processes. For instance, it is used in cardiac function, contraction of muscles, neurotransmission, platelet function, metabolism of glycogen, and vasodilation [Franzini-Armstrong, 2014]. Additionally, the mitochondrial functions are involved in the synthesis of RNA and DNA. Some chemical substances such as thyroid hormone have a direct effect on the mitochondria and thus regulate energy transformation into forms usable by the cell. In this regard, hypothyroidism leads to slower oxygen consumption due to derailed respiration while hyperthyroidism leads to faster consumption. Additionally, according to O'rourke , increased thyroid function may lead to oxidative tissue injury which may lead to mitochondrial damage. However, thyroid hormone is associated with mitochondrial mechanisms that protect cells against tissue dysfunction [Romanello and Sandri, 2016]. Also, the hormone increases the oxidative capacity of the cells by stimulating mitochondriogenesis. Therefore, the primary cause of death of a cell is inadequate cellular ATP due to dysfunction of the organelle. Therefore, failure of the mitochondria in skeletal muscles may lead to weakness and inability to contract muscles.
The mitochondrial damage that may lead to cell death is caused by the free radicals produced during the metabolic processes or other toxins. For instance, according to O'rourke , studies have indicated that thimerosal-derived ethylmercury, usually found in some skin antigen tests or vaccines as a preservative, can cause inhibition of mitochondrial respiration. Consequently, this substance causes increased formation of superoxide that may damage the organelle. Several pathogens such as clostridium difficile and H. pylori have also been associated with mitochondrial damage [Franzini-Armstrong, 2014]. Therefore, these toxins may lead to mitochondrial myopathy that affects a range of body systems which may lead to dysfunction of the whole body.
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