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A mitochondrion is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name.
Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient. This process is in contrast to passive transport, which allows molecules or ions to move down their concentration gradient, from an area of high concentration to an area of low concentration, without energy.
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released into the cell when necessary and then removed from the cell.
Uniporters, also known as solute carriers or facilitated transporters, are a type of membrane transport protein that passively transports solutes across a cell membrane. It uses facilitated diffusion for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration. Unlike active transport, it does not require energy in the form of ATP to function. Uniporters are specialized to carry one specific ion or molecule and can be categorized as either channels or carriers. Facilitated diffusion may occur through three mechanisms: uniport, symport, or antiport. The difference between each mechanism depends on the direction of transport, in which uniport is the only transport not coupled to the transport of another solute.
In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate.
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. It also refers to the space between the inner and outer nuclear membranes of the nuclear envelope, but is often called the perinuclear space. The IMS of mitochondria plays a crucial role in coordinating a variety of cellular activities, such as regulation of respiration and metabolic functions. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function.
Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin, an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of life. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from trans form to cis form at proline residues and facilitates protein folding.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
The mitochondrial permeability transition pore is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. Opening allows increase in the permeability of the mitochondrial membranes to molecules of less than 1500 daltons in molecular weight. Induction of the permeability transition pore, mitochondrial membrane permeability transition, can lead to mitochondrial swelling and cell death through apoptosis or necrosis depending on the particular biological setting.
The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions (Ca2+). A single calcium ion is exported for the import of three sodium ions. The exchanger exists in many different cell types and animal species. The NCX is considered one of the most important cellular mechanisms for removing Ca2+.
The inorganic dye ammoniated ruthenium oxychloride, also known as ruthenium red, is used in histology to stain aldehyde fixed mucopolysaccharides.
Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered.
Coiled-coil domain containing 109B (CCDC109B) is a potential calcium uniporter protein found in the membrane of human cells and is encoded by the CCDC109B gene. While CCDC109B is a transmembrane protein it is unclear if it is located within the cell membrane or mitochondrial membrane.
Histidine triad nucleotide binding protein 2 (HINT2) is a mitochondrial protein that in humans is encoded by the HINT2 gene on chromosome 9. This protein is an AMP-lysine hydrolase and phosphoamidase and may contribute to tumor suppression.
Ru360 is an oxo-bridged dinuclear ruthenium ammine complex with an absorption spectrum maximum at 360 nm. It is an analog of ruthenium red, a well-known effective inhibitor of the mitochondrial calcium uniporter.
Mitochondria-associated membranes (MAMs) represent regions of the endoplasmic reticulum (ER) which are reversibly tethered to mitochondria. These membranes are involved in import of certain lipids from the ER to mitochondria and in regulation of calcium homeostasis, mitochondrial function, autophagy and apoptosis. They also play a role in development of neurodegenerative diseases and glucose homeostasis.
References
- ↑ "MCU - Calcium uniporter protein, mitochondrial precursor - Homo sapiens (Human)". UniProt.org. UniProt Consortium. Retrieved 2016-02-24.
- 1 2 3 4 5 Marchi S, Pinton P (March 2014). "The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications". The Journal of Physiology. 592 (5): 829–839. doi:10.1113/jphysiol.2013.268235. PMC 3948548 . PMID 24366263.
- ↑ Broekemeier KM, Krebsbach RJ, Pfeiffer DR (October 1994). "Inhibition of the mitochondrial Ca2+ uniporter by pure and impure ruthenium red". Molecular and Cellular Biochemistry. 139 (1): 33–40. doi:10.1007/bf00944201. PMID 7531818. S2CID 516473.
- ↑ Matlib MA, Zhou Z, Knight S, Ahmed S, Choi KM, Krause-Bauer J, et al. (April 1998). "Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes". The Journal of Biological Chemistry. 273 (17): 10223–10231. doi: 10.1074/jbc.273.17.10223 . PMID 9553073.
- ↑ Kamer KJ, Sancak Y, Fomina Y, Meisel JD, Chaudhuri D, Grabarek Z, et al. (August 2018). "MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca2+ and Mn2+". Proceedings of the National Academy of Sciences of the United States of America. 115 (34): E7960–E7969. Bibcode:2018PNAS..115E7960K. doi: 10.1073/pnas.1807811115 . PMC 6112746 . PMID 30082385.
- ↑ Wettmarshausen J, Goh V, Huang KT, Arduino DM, Tripathi U, Leimpek A, et al. (November 2018). "MICU1 Confers Protection from MCU-Dependent Manganese Toxicity" (PDF). Cell Reports. 25 (6): 1425–1435.e7. doi:10.1016/j.celrep.2018.10.037. PMID 30403999. S2CID 53209158.
- ↑ Monteith AJ, Miller JM, Beavers WN, Maloney KN, Seifert EL, Hajnoczky G, et al. (December 2021). "Mitochondrial calcium uniporter affects neutrophil bactericidal activity during Staphylococcus aureus infection". Infection and Immunity. 90 (2): IAI0055121. doi:10.1128/IAI.00551-21. PMC 8853686 . PMID 34871043.