The mitochodrion contains inner and outer membranes composed of phospholipid bilayers and proteins. The two membranes, however, have different properties. Because of this double-membraned organization, there are 5 distinct compartments within mitochondria. There is the outer membrane, the intermembrane space (the space between the outer and inner membranes), the inner membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane). Mitochondria range from 1 to 10 micrometers (µm) in size.
Outer membrane
The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane (about 1:1 by weight). It contains numerous integral proteins called porins.
Intermembrane space
The intermembrane space is the space between the outer membrane and the inner membrane.
Inner membrane
The inner mitochondrial membrane contains proteins with four types of functions: [2]
- Those that carry out the oxidation reactions of the respiratory chain.
- ATP synthase, which makes ATP in the matrix.
- Specific transport proteins that regulate the passage of metabolites into and out of the matrix.
- Protein import machinery.
It contains more than 100 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). Additionally the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in beef hearts in 1942 and is usually characteristic of mitochondrial and bacterial plasma membranes.[4] Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable; almost all ions and molecules require special membrane transporters to enter or exit the matrix. In addition, there is a membrane potential across the inner membrane.
The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to generate ATP. In typical liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. Mitochondria of cells which have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria.
Mitochondrial matrix
Image of cristae in rat liver mitochondrion
The matrix is the space enclosed by the inner membrane. The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, in addition to the special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNAgenome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.[2]
Mitochondria possess their own genetic material, and the machinery to manufacture their own RNAs and proteins. (See: protein synthesis). A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes, 24 tRNA and rRNA genes and 13 peptide genes.[5] The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus.
Mitochondrial functions
Although it is well known that the mitochondria convert organic materials into cellular energy in the form of ATP, mitochondria play an important role in many metabolic tasks, such as:
Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.
Energy conversion
A dominant role for the mitochondria is the production of ATP as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glycolysis: pyruvate and NADH that are produced in the cytosol. This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. When oxygen is limited the glycolytic products will be metabolised by anaerobic respiration, a process that is independent of the mitochondria. The production of ATP from glucose has an approximately 15 fold higher yield during aerobic respiration compared to anaerobic respiration.
Pyruvate: the citric acid cycle
Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO2, acetyl-CoA and NADH.
The acetyl-CoA is the primary substrate to enter the citric acid cycle , also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. The enzymes of the citric acid cycle are located in the mitochondrial matrix with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane. The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide and in the process produces reduced cofactors (three molecules of NADH and one molecule of FADH2), that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP).
NADH and FADH2: the electron transport chain
The redox energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transport chain. These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis; reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle. Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H+) into the intermembrane space. This process is efficient but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process.[6]
As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis and was first described by Peter Mitchell[7][8] who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.
Heat production
Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. This process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. The process is mediated by a proton channel called thermogenin, or UCP1.[9] Thermogenin is a 33kDa protein first discovered in 1973.[10] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age.[9]
