ATP Synthesis
The primary and most important function of Mitochondria is the synthesis of energy (ATP Synthesis) and ATP synthesis takes place through Aerobic Cellular Respiration. As the name shows, it is dependent on the presence of oxygen as the Mitochondria play an important role in the synthesis of energy Seikevitz proposed it as the “Power house of the cell” in 1957.
- Aerobic cellular respiration takes place in three main steps.
Glycolysis
- It is the metabolic pathway that converts glucose into pyruvate within the cytoplasm of a cell. The glycolysis produces the pyruvate and NADH in the cytosol.
- In the absence of oxygen, NADH reduced the pyruvate to lactate. As the process of glycolysis continues the NAD+ which is formed during the reaction is utilized.
- In the presence of oxygen, a large amount of energy is extracted from the pyruvate. NADH is produced during glycolysis, and this is enough to produce more than 30 ATP molecules and this energy is extracted in the mitochondria. Pyruvate can diffuse into the inner mitochondrial matrix under aerobic conditions (in the presence of oxygen) with the help of a membrane transporter where it is decarboxylated to form a two-carbon acetyl group and bind with the Acetyl coenzyme A (CoA), a reaction that generates NADH. Pyruvate Dehydrogenase is a multi enzyme complex that causes the decarboxylation of the pyruvate and transfer of the acetyl group to CoA along with the reduction of NAD+.
Glycerol Phosphate Shuttle
- Mitochondria are unable to import the NADH formed in the cytosol during glycolysis. Instead, the electrons of cytosolic NADH are used to reduce a low molecular weight metabolite that can enter the mitochondria by transferring its electrons to FAD by a pathway called Glycerol phosphate shuttle. NADH produced during glycolysis donates its high energy electrons to a compound that has the ability to cross the inner mitochondrial membrane.
- The electrons are transferred from NADH to dihydroxyacetone phosphate (DHAP) to produce glycerol 3-phosphate with the help of the Glycerol phosphate shuttle, which transfers them into the mitochondria. Glycerol-3-phosphate hydrogenase catalyzes the oxidation of G3P regenerating DHAP in the cytosol and forming FADH2 in the mitochondrial matrix. At the inner mitochondrial matrix, these electrons then reduced the FAD as a result FADH2 produce which then can transfer the electrons to the carrier of the electron transport chain.
Krebs Cycle
- The Acetyl CoA then passes through the TCA cycle (Tricarboxylic acid Cycle) to generate NADH and FADH2.In this cycle, the substrate is oxidized and energy is conserved. All the enzymes of the TCA cycle reside in the soluble phase of the matrix except the Succinate dehydrogenase which is bound to the inner membrane. The TCA cycle is referred to as Krebs Cycle.
- Krebs cycle itself begins when acetyl- CoA combines with four carbon molecules called oxaloacetate. As a result, Citric acid is produced which is six carbon atoms, that’s why Krebs Cycle is also called the Citric Acid cycle. The TCA cycle occurs in the mitochondria during aerobic respiration to release energy through the oxidation process.
- During the cycle, the citrate molecule is reduced in its chain length, at a time one carbon, regenerating the four carbon oxaloacetate molecules and again condensed with acetyl CoA. It is the two carbons that are completely removed during the TCA cycle and oxidized to carbon dioxide completely. Four reactions occur in which pair of electrons are transferred from substrate to electron accepting co-enzyme in which three of the reactions reduced the NAD+ into NADH and one reaction reduced FAD to FADH2.
- The primary products of the TCA cycle are reduced co-enzymes FADH2 and NADH which contains the high energy molecules which are removed from various substrates when they are oxidized.
Electron Transport Chain (in Mitochondria) and Oxidative phosphorylation (ATP Synthesis)
- Oxidative Phosphorylation has two parts; the Electron Transport Chain and the Chemiosmosis. The Electron transport chain consists of a number of proteins that are bound with the mitochondrial inner membrane where the electrons are passed through a series of redox reactions and release energy. The ETC is highly coupled to the process of oxidative phosphorylation with the help of the ATP synthase system for the production of energy in the form of ATP.
- ETC is made up of a series of electron carriers located in the mitochondrial inner membrane. High energy electrons pass through the first series of the electron carriers that make up the electron transport chain. These electrons release energy reactions. There is much energy requiring conformational changes to take place in these electron carriers that moves the electrons outside the inner mitochondrial membrane as a result a proton electrochemical gradient across the inner mitochondrial membrane is established. With the help of the ATP synthesis complex, the protons move down the electrochemical gradient. ATP synthesis takes place by this stored energy in the gradient.
Synthesis of Protein and RNAs
Mitochondria play various roles as an independent unit. Within a Eukaryotic cell, Mitochondria have their own Genetic Material (contains 2-6 circular DNA) so they can replicate themselves and the Machinery of protein synthesis (contains Ribosomes and RNAs) that’s why it works independently of the cell in which it is present and can synthesize the proteins and RNAs.
Mitochondrial genes can code for a number of proteins that are acting as enzymes for their metabolic activities. There are 13 proteins that are coded by the 37 genes. Mitochondrial genes and mutation in genes cause certain mitochondrial diseases. Mitochondrial DNA is maternally inherited.
Programmed cell death
- Mitochondria play an important role in Programmed Cell Death. As the cells become old or broken they are cleared and destroyed. Mitochondria help to decide which cells are to be destroyed. Apoptosis is a form of programmed cell death in multicellular organisms which is normal cell death and considered a controlled part of Human development and growth.
- Caspase is an enzyme that plays an important role in destroying the cell during apoptosis and this enzyme is activated by Cytochrome C which is released by Mitochondria. Cytochromes are present in the cytosol or intracellular fluid of eukaryotic cells.
Photorespiration
- Along with normal respiratory functions plants mitochondria play an important role in photorespiration. It is light dependent uptake of molecular oxygen with the release of carbon dioxide from the organic compound. It is a wasteful process that results in the loss of the CO2 fixed by the plants. In the leaves of C3 plants, in mesophyll cells, mitochondria play an important role in photorespiration. There are three cell organelles involved in it i.e Chloroplast, peroxisome, and Mitochondria.
- Under the high level of oxygen, Ribulose 1,5-diphosphate reacts with oxygen instead of CO2 with the help of an enzyme called RUBISCO which forms 3PGA and 2C Phosphoglycolic acid and then diffuses to peroxisome from the mitochondria where it is converted to glycine which then passes to the mitochondria.
- Two molecules of Glycine are converted to one molecule of serine releasing one molecule of carbon dioxide and HN3. There is no synthesis of the ATP and NADPH.
Storage of Calcium
Mitochondria also play an important role in the Storage of Calcium. Calcium plays a very important role in maintaining the physiology and biochemistry of cells for example in blood clotting, contraction of the muscles and fertilization, neurotransmitters release from the neurons, and in the signal transduction pathways. Mitochondria quickly absorb the calcium ions and hold them until they are needed. At the cellular level, calcium is held by two types of organelles. One is the Mitochondria and Endoplasmic Reticulum.
Role in Innate immunity
- Mitochondria are the critical organelles that play an important role to regulate the Immune system. The innate immune system is the first part of the body to detect viruses, bacteria, toxins, and parasites. Mitochondria contain a protein Mitochondria antiviral signaling protein (MAVS) plays an important role in the innate response to viral infections.
- The mitochondria facilitate antibacterial immunity by generating the Reacting oxygen species. The regeneration potential of the Human bone marrow that is essential for making skeletal tissues, such as cartilage and bone is reduced by the increase in Reactive Oxygen species (ROS) generated by the mitochondria.
Function in specific types of cells
The liver is the major organ that performs the detoxification of harmful substances For example, Ammonia is the waste product of protein metabolism. Mitochondria in the liver cells contain the enzyme which causes the detoxification of ammonia. Similarly, the enzymes required for lipids, cholesterol, amino acid synthesis, and hormones are also synthesized in the mitochondria.
References
Iwasa, J., Marshall W.F., and Karp, G.(2020). Karp’s cell and Molecular Biology: Concepts and Experiments.Wiley.
