| Cell biology | |
|---|---|
| mitochondrion | |
 Components of a typical mitochondrion
3 Lamella
4 Mitochondrial DNA Contents
|
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
| Cell biology | |
|---|---|
| mitochondrion | |
| Components of a typical mitochondrion
3 Lamella
4 Mitochondrial DNA Contents
|
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. The numerous invaginations of the membrane are called cristae, separated by crista junctions from the inner boundary membrane juxtaposed to the outer membrane. Cristae significantly increase the total membrane surface area compared to a smooth inner membrane and thereby the available working space for oxidative phosphorylation.
The inner membrane creates two compartments. The region between the inner and outer membrane, called the intermembrane space, is largely continuous with the cytosol, while the more sequestered space inside the inner membrane is called the matrix.
For typical liver mitochondria, the area of the inner membrane is about 5 times as large as the outer membrane due to cristae. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Cristae membranes are studded on the matrix side with small round protein complexes known as F1 particles, the site of proton-gradient driven ATP synthesis. Cristae affect overall chemiosmotic function of mitochondria. [1]
Cristae and the inner boundary membranes are separated by junctions. The end of cristae are partially closed by transmembrane protein complexes that bind head to head and link opposing crista membranes in a bottleneck-like fashion. [2] For example, deletion of the junction protein IMMT leads to a reduced inner membrane potential and impaired growth [3] and to dramatically aberrant inner membrane structures which form concentric stacks instead of the typical invaginations. [4]
The inner membrane of mitochondria is similar in lipid composition to the membrane of bacteria. This phenomenon can be explained by the endosymbiont hypothesis of the origin of mitochondria as prokaryotes internalized by a eukaryotic host cell.
In pig heart mitochondria, phosphatidylethanolamine makes up the majority of the inner mitochondrial membrane at 37.0% of the phospholipid composition. Phosphatidylcholine makes up about 26.5%, cardiolipin 25.4%, and phosphatidylinositol 4.5%. [5] In S. cerevisiae mitochondria, phosphatidylcholine makes up 38.4% of the IMM, phosphatidylethanolamine makes up 24.0%, phosphatidylinositol 16.2%, cardiolipin 16.1%, phosphatidylserine 3.8%, and phosphatidic acid 1.5%. [6]
In the inner mitochondrial membrane, the protein-to-lipid ratio is 80:20, in contrast to the outer membrane, which is 50:50. [7]
The inner membrane is freely permeable to oxygen, carbon dioxide, and water only. [8] It is much less permeable to ions and small molecules than the outer membrane, creating compartments by separating the matrix from the cytosolic environment. This compartmentalization is a necessary feature for metabolism. The inner mitochondrial membrane is both an electrical insulator and chemical barrier. Sophisticated ion transporters exist to allow specific molecules to cross this barrier. There are several antiport systems embedded in the inner membrane, allowing exchange of anions between the cytosol and the mitochondrial matrix. [7]
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.
Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this electron transfer with the transfer of protons (H+ ions) across a membrane. Many of the enzymes in the electron transport chain are embedded within the membrane.
A crista is a fold in the inner membrane of a mitochondrion. The name is from the Latin for crest or plume, and it gives the inner membrane its characteristic wrinkled shape, providing a large amount of surface area for chemical reactions to occur on. This aids aerobic cellular respiration, because the mitochondrion requires oxygen. Cristae are studded with proteins, including ATP synthase and a variety of cytochromes.
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.
Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most bacteria. The name "cardiolipin" is derived from the fact that it was first found in animal hearts. It was first isolated from the beef heart in the early 1940s by Mary C. Pangborn. In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane, where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.
In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.
Tafazzin is a protein that in humans is encoded by the TAFAZZIN gene. Tafazzin is highly expressed in cardiac and skeletal muscle, and functions as a phospholipid-lysophospholipid transacylase. It catalyzes remodeling of immature cardiolipin to its mature composition containing a predominance of tetralinoleoyl moieties. Several different isoforms of the tafazzin protein are produced from the TAFAZZIN gene. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. Most isoforms are found in all tissues, but some are found only in certain types of cells. Mutations in the TAFAZZIN gene have been associated with mitochondrial deficiency, Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, left ventricular noncompaction (LVNC), breast cancer, papillary thyroid carcinoma, non-small cell lung cancer, glioma, gastric cancer, thyroid neoplasms, and rectal cancer.
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are members of the general family of transmembrane lipid transporters known as flippases. Scramblases are distinct from flippases and floppases. Scramblases, flippases, and floppases are three different types of enzymatic groups of phospholipid transportation enzymes. The inner-leaflet, facing the inside of the cell, contains negatively charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, that can transport (scramble) the negatively charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa.
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.
Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine can subsequently methylate the amine of phosphatidylethanolamines to yield phosphatidylcholines.
Adenine nucleotide translocator (ANT), also known as the ADP/ATP translocase (ANT), ADP/ATP carrier protein (AAC) or mitochondrial ADP/ATP carrier, exchanges free ATP with free ADP across the inner mitochondrial membrane. ANT is the most abundant protein in the inner mitochondrial membrane and belongs to mitochondrial carrier family.
Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.
The translocase of the outer membrane (TOM) is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. It allows movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial function are encoded by the nucleus of the cell. The outer membrane of the mitochondrion is impermeable to large molecules greater than 5000 daltons. The TOM works in conjunction with the translocase of the inner membrane (TIM) to translocate proteins into the mitochondrion. Many of the proteins in the TOM complex, such as TOMM22, were first identified in Neurospora crassa and Saccharomyces cerevisiae. Many of the genes encoding these proteins are designated as TOMM (translocase of the outer mitochondrial membrane) complex genes.
The translocase of the inner membrane (TIM) is a complex of proteins found in the inner mitochondrial membrane of the mitochondria. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the mitochondrial matrix. They also facilitate the insertion of proteins into the inner mitochondrial membrane, where they must reside in order to function, these mainly include members of the mitochondrial carrier family of proteins.
Mitochondria are dynamic organelles with the ability to fuse and divide (fission), forming constantly changing tubular networks in most eukaryotic cells. These mitochondrial dynamics, first observed over a hundred years ago are important for the health of the cell, and defects in dynamics lead to genetic disorders. Through fusion, mitochondria can overcome the dangerous consequences of genetic malfunction. The process of mitochondrial fusion involves a variety of proteins that assist the cell throughout the series of events that form this process.
Mitochondria-associated membranes (MAM) represent a region of the endoplasmic reticulum (ER) which is 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.
The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.