Misplaced Pages

#700299

68-500: AGE was founded in 1970 by Denham Harman , MD, PhD, who is often known as the "father" of the " free-radical theory of aging ". Harman's goal was to form a lay-scientific organization patterned after the American Heart Association to promote biomedical aging research. Harman served as the first president of AGE, and was executive director of AGE for 20 years (1973 to 1993). AGE has received research grants from

136-485: A liver cell can have more than 2000. The mitochondrion is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, intermembrane space , inner membrane , cristae , and matrix . Although most of a eukaryotic cell's DNA is contained in the cell nucleus , the mitochondrion has its own genome ("mitogenome") that is substantially similar to bacterial genomes. This finding has led to general acceptance of

204-416: 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. Meaning a thread-like granule, the term mitochondrion was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of

272-462: A fundamental role in immunity by aiding in antiviral defense, pathogen elimination, inflammation, and immune cell recruitment. Mitochondria have long been recognized for their central role in the intrinsic pathway of apoptosis , a form of PCD. In recent decades, they have also been identified as a signalling hub for much of the innate immune system . The endosymbiotic origin of mitochondria distinguishes them from other cellular components, and

340-568: A large multisubunit protein called translocase in the outer membrane , which then actively moves them across the membrane. Mitochondrial pro-proteins are imported through specialised translocation complexes. The outer membrane also contains enzymes involved in such diverse activities as the elongation of fatty acids , oxidation of epinephrine , and the degradation of tryptophan . These enzymes include monoamine oxidase , rotenone -insensitive NADH-cytochrome c-reductase, kynurenine hydroxylase and fatty acid Co-A ligase . Disruption of

408-465: A limited amount of ATP either by breaking the sugar produced during photosynthesis or without oxygen by using the alternate substrate nitrite . ATP crosses out through the inner membrane with the help of a specific protein , and across the outer membrane via porins . After conversion of ATP to ADP by dephosphorylation that releases energy, ADP returns via the same route. Pyruvate molecules produced by glycolysis are actively transported across

476-1255: A lot of free energy from the reactants without breaking bonds of an organic fuel. The free energy put in to remove an electron from Fe is released at complex III when Fe of cytochrome c reacts to oxidize ubiquinol (QH 2 ): 2 Fe 3 + ( cyt c ) + QH 2 ⟶ 2 Fe 2 + ( cyt c ) + Q + 2 H + ( aq ) {\displaystyle {\ce {2Fe^{3+}(cyt\,c){}+QH2->2Fe^{2+}(cyt\,c){}+Q{}+2H+(aq)}}} Δ r G o ′ = − 30  kJ/mol {\displaystyle \Delta _{r}G^{o'}=-30{\text{ kJ/mol}}} The ubiquinone (Q) generated reacts, in complex I , with NADH: Q + H + ( aq ) + NADH ⟶ QH 2 + NAD + {\displaystyle {\ce {Q + H+(aq){}+ NADH -> QH2 + NAD+ {}}}} Δ r G o ′ = − 81  kJ/mol {\displaystyle \Delta _{r}G^{o'}=-81{\text{ kJ/mol}}} While

544-520: A mitochondrion: Mitochondria have folding to increase surface area, which in turn increases ATP (adenosine triphosphate) production. Mitochondria stripped of their outer membrane are called mitoplasts . The outer mitochondrial membrane , which encloses the entire organelle, is 60 to 75 angstroms (Å) thick. It has a protein-to-phospholipid ratio similar to that of the cell membrane (about 1:1 by weight). It contains large numbers of integral membrane proteins called porins . A major trafficking protein

612-700: A reduction of oxidative stress . In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase , one of the key regulatory enzymes of the Krebs cycle . The relationship between cellular proliferation and mitochondria has been investigated. Tumor cells require ample ATP to synthesize bioactive compounds such as lipids , proteins , and nucleotides for rapid proliferation. The majority of ATP in tumor cells

680-554: A technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAM—the interface between mitochondria and the ER. Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy . Such studies estimate that at

748-517: A very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. Additionally, the inner membrane is rich in an unusual phospholipid, cardiolipin . This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. Cardiolipin contains four fatty acids rather than two, and may help to make

SECTION 10

#1732790750701

816-427: A waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases . Mitochondrial proteins (proteins transcribed from mitochondrial DNA) vary depending on the tissue and the species. In humans, 615 distinct types of proteins have been identified from cardiac mitochondria, whereas in rats , 940 proteins have been reported. The mitochondrial proteome

884-540: A weight of 140 pounds on his 5-foot-10 frame. Harman died in Omaha, Nebraska , on November 25, 2014, from a short illness, aged 98. In 1954, between his internship and residency in internal medicine , Harman became a research associate at the Donner Laboratory of Medical Physics at UC Berkeley , where he was able to pursue the puzzle of the cause of aging . After four months of frustration he hit upon

952-500: Is a significant interplay between the mitochondrion and ER with regard to calcium. The calcium is taken up into the matrix by the mitochondrial calcium uniporter on the inner mitochondrial membrane . It is primarily driven by the mitochondrial membrane potential . Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways. This can initiate calcium spikes or calcium waves with large changes in

1020-489: Is called chemiosmosis , and was first described by Peter Mitchell , 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. Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process

1088-457: Is generated via the oxidative phosphorylation pathway (OxPhos). Interference with OxPhos cause cell cycle arrest suggesting that mitochondria play a role in cell proliferation. Mitochondrial ATP production is also vital for cell division and differentiation in infection in addition to basic functions in the cell including the regulation of cell volume, solute concentration , and cellular architecture. ATP levels differ at various stages of

1156-401: Is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The 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 . Thermogenin is primarily found in brown adipose tissue , or brown fat, and

1224-458: Is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO 2 and water, with the energy thus released captured in the form of ATP. In the liver, the carboxylation of cytosolic pyruvate into intra-mitochondrial oxaloacetate is an early step in the gluconeogenic pathway, which converts lactate and de-aminated alanine into glucose, under the influence of high levels of glucagon and/or epinephrine in

1292-561: Is often found in unicellular organisms, while human liver cells have about 1000–2000 mitochondria per cell, making up 1/5 of the cell volume. The mitochondrial content of otherwise similar cells can vary substantially in size and membrane potential, with differences arising from sources including uneven partitioning at cell division, leading to extrinsic differences in ATP levels and downstream cellular processes. The mitochondria can be found nestled between myofibrils of muscle or wrapped around

1360-454: 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. Mitochondrial fatty acid synthesis (mtFASII) is essential for cellular respiration and mitochondrial biogenesis. It is also thought to play a role as a mediator in intracellular signaling due to its influence on

1428-425: Is the pore-forming voltage-dependent anion channel (VDAC). The VDAC is the primary transporter of nucleotides , ions and metabolites between the cytosol and the intermembrane space. It is formed as a beta barrel that spans the outer membrane, similar to that in the gram-negative bacterial outer membrane . Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to

SECTION 20

#1732790750701

1496-400: Is the space enclosed by the inner membrane. It contains about 2/3 of the total proteins in a mitochondrion. 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, special mitochondrial ribosomes , tRNA , and several copies of the mitochondrial DNA genome . Of

1564-573: Is thought to be dynamically regulated. Mitochondria (or related structures) are found in all eukaryotes (except the Oxymonad Monocercomonoides ). Although commonly depicted as bean-like structures they form a highly dynamic network in the majority of cells where they constantly undergo fission and fusion . The population of all the mitochondria of a given cell constitutes the chondriome. Mitochondria vary in number and location according to cell type. A single mitochondrion

1632-485: The N -formylation of mitochondrial proteins , similar to that of bacterial proteins, can be recognized by formyl peptide receptors . Normally, these mitochondrial components are sequestered from the rest of the cell but are released following mitochondrial membrane permeabilization during apoptosis or passively after mitochondrial damage. However, mitochondria also play an active role in innate immunity, releasing mtDNA in response to metabolic cues. Mitochondria are also

1700-617: The National Institutes of Health and the Ellison Medical Foundation . In 2016, AGE became a member of the Federation of American Societies for Experimental Biology . The vice-presidency of AGE is to be a layperson position focused on promoting the scientific goals of AGE to the general public. The primary activities of AGE are to: The journal of AGE is GeroScience . Formerly called AGE ,

1768-445: The cell cycle and cell growth . Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes. Mitochondria have been implicated in several human disorders and conditions, such as mitochondrial diseases , cardiac dysfunction , heart failure and autism . The number of mitochondria in a cell can vary widely by organism , tissue , and cell type. A mature red blood cell has no mitochondria, whereas

1836-421: The citric acid cycle , or the Krebs cycle, and oxidative phosphorylation . However, the mitochondrion has many other functions in addition to the production of ATP. 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 glucose : pyruvate , and NADH , which are produced in

1904-463: The cytosol . However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol . One protein that is localized to the intermembrane space in this way is cytochrome c . The inner mitochondrial membrane contains proteins with three types of functions: It contains more than 151 different polypeptides , and has

1972-564: The endosymbiotic hypothesis - that free-living prokaryotic ancestors of modern mitochondria permanently fused with eukaryotic cells in the distant past, evolving such that modern animals, plants, fungi, and other eukaryotes are able to respire to generate cellular energy . Mitochondria may have a number of different shapes. A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins . The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to

2040-404: The glycine cleavage system (GCS), mtFASII has an influence on energy metabolism. Other products of mtFASII play a role in the regulation of mitochondrial translation, FeS cluster biogenesis and assembly of oxidative phosphorylation complexes. Furthermore, with the help of mtFASII and acylated ACP, acetyl-CoA regulates its consumption in mitochondria. The concentrations of free calcium in

2108-514: The localization site for immune and apoptosis regulatory proteins, such as BAX , MAVS (located on the outer membrane ), and NLRX1 (found in the matrix ). These proteins are modulated by the mitochondrial metabolic status and mitochondrial dynamics. Mitochondria play a central role in many other 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 ,

American Aging Association - Misplaced Pages Continue

2176-446: The sperm flagellum . Often, they form a complex 3D branching network inside the cell with the cytoskeleton . The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well: different structures of the mitochondrial network may afford the population a variety of physical, chemical, and signalling advantages or disadvantages. Mitochondria in cells are always distributed along microtubules and

2244-598: The College of Chemistry at the University of California, Berkeley and his M.D. from Stanford University , finishing his internship in 1954. Immediately after earning his Ph.D., in 1943, Harman joined the reaction kinetics department of Shell Oil in Emeryville, California . He worked for six years as a Shell research chemist , in part studying free radical reactions in petroleum products. During that period he

2312-565: The MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated 'powerhouses' hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to

2380-594: The MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10–25 nm and held together by protein tethering complexes. Purified MAM from subcellular fractionation is enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca signaling. These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has

2448-510: The area of the inner membrane is about five times as large as that of the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Mitochondria within the same cell can have substantially different crista-density, with the ones that are required to produce more energy having much more crista-membrane surface. These folds are studded with small round bodies known as F 1 particles or oxysomes. The matrix

2516-417: The blood. Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted to cytosolic oxaloacetate, and ultimately to glucose, in a process that is almost the reverse of glycolysis . The enzymes of the citric acid cycle are located in the mitochondrial matrix, with

2584-632: The cause of aging. In 1970 he became a founder of the American Aging Association (AGE) to create a society of scientists focused on aging research and advocacy of aging research. In 1985 he became a founder of the International Association of Biomedical Gerontology (IABG). Mitochondria A mitochondrion ( pl.   mitochondria ) is an organelle found in the cells of most eukaryotes , such as animals , plants and fungi . Mitochondria have

2652-410: The cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium , a contributing process for the cell's homeostasis of calcium. Their ability to rapidly take in calcium for later release makes them good "cytosolic buffers" for calcium. The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there

2720-440: The cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle. ATP's role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP. The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation. Although

2788-1094: The cell", a phrase popularized by Philip Siekevitz in a 1957 Scientific American article of the same name. Some cells in some multicellular organisms lack mitochondria (for example, mature mammalian red blood cells ). The multicellular animal Henneguya salminicola is known to have retained mitochondrion-related organelles despite a complete loss of their mitochondrial genome. A large number of unicellular organisms , such as microsporidia , parabasalids and diplomonads , have reduced or transformed their mitochondria into other structures, e.g. hydrogenosomes and mitosomes . The oxymonads Monocercomonoides , Streblomastix , and Blattamonas have completely lost their mitochondria. Mitochondria are commonly between 0.75 and 3  μm in cross section, but vary considerably in size and structure. Unless specifically stained , they are not visible. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling , cellular differentiation , and cell death , as well as maintaining control of

American Aging Association - Misplaced Pages Continue

2856-436: The cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases

2924-452: The cytosol. This type of cellular respiration , known as aerobic respiration , is dependent on the presence of oxygen . When oxygen is limited, the glycolytic products will be metabolized by anaerobic fermentation , a process that is independent of the mitochondria. The production of ATP from glucose and oxygen has an approximately 13-times higher yield during aerobic respiration compared to fermentation. Plant mitochondria can also produce

2992-425: The distribution of these organelles is also correlated with the endoplasmic reticulum . Recent evidence suggests that vimentin , one of the components of the cytoskeleton, is also critical to the association with the cytoskeleton. The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis . Once considered

3060-426: The endomembrane system. The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face. Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity. But mitochondria are not only

3128-470: The enzymes, the major functions include oxidation of pyruvate and fatty acids , and the citric acid cycle . The DNA molecules are packaged into nucleoids by proteins, one of which is TFAM . The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP (i.e., phosphorylation of ADP ), through respiration and to regulate cellular metabolism . The central set of reactions involved in ATP production are collectively known as

3196-620: The exception of succinate dehydrogenase , which is bound to the inner mitochondrial membrane as part of Complex II. 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 FADH 2 ) that are a source of electrons for the electron transport chain , and a molecule of GTP (which is readily converted to an ATP). The electrons from NADH and FADH 2 are transferred to oxygen (O 2 ) and hydrogen (protons) in several steps via an electron transport chain. NADH and FADH 2 molecules are produced within

3264-453: The exposure of mitochondrial elements to the cytosol can trigger the same pathways as infection markers. These pathways lead to apoptosis , autophagy , or the induction of proinflammatory genes. Mitochondria contribute to apoptosis by releasing cytochrome c , which directly induces the formation of apoptosomes . Additionally, they are a source of various damage-associated molecular patterns (DAMPs). These DAMPs are often recognised by

3332-585: The idea of free radicals as cause of the damage to macromolecules known as " aging ". Although initially other scientists were reluctant to accept his theory, he was finally able to get it published in what is now a much-cited article in the Journal of Gerontology. After years of frustration over his inability to increase maximum lifespan with antioxidant supplements, Harman came to the conclusion that mitochondria were producing as well as being damaged by free radicals, but that exogenous antioxidants don't enter

3400-549: The inner membrane (TIM) complex or via OXA1L . In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain . Inner membrane fusion is mediated by the inner membrane protein OPA1 . The inner mitochondrial membrane is compartmentalized into numerous folds called cristae , which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria,

3468-410: The inner membrane impermeable, and its disruption can lead to multiple clinical disorders including neurological disorders and cancer. Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of

SECTION 50

#1732790750701

3536-785: The inner mitochondrial membrane ( NADH dehydrogenase (ubiquinone) , cytochrome c reductase , and cytochrome c oxidase ). At complex IV , O 2 reacts with the reduced form of iron in cytochrome c : O 2 + 4 H + ( aq ) + 4 Fe 2 + ( cyt c ) ⟶ 2 H 2 O + 4 Fe 3 + ( cyt c ) {\displaystyle {\ce {O2{}+4H+(aq){}+4Fe^{2+}(cyt\,c)->2H2O{}+4Fe^{3+}(cyt\,c)}}} Δ r G o ′ = − 218  kJ/mol {\displaystyle \Delta _{r}G^{o'}=-218{\text{ kJ/mol}}} releasing

3604-434: The inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO 2 , acetyl-CoA , and NADH , or they can be carboxylated (by pyruvate carboxylase ) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle and is therefore an anaplerotic reaction , increasing the cycle's capacity to metabolize acetyl-CoA when

3672-493: The journal name was officially changed at the beginning of 2017. Conferences Denham Harman Denham Harman (February 14, 1916 – November 25, 2014) was an American medical academic who latterly served as professor emeritus at the University of Nebraska Medical Center . Harman is known as the " father of the free radical theory of aging ". Born in San Francisco, he earned his BS and Ph.D. in 1943 from

3740-483: The levels of bioactive lipids, such as lysophospholipids and sphingolipids . Octanoyl-ACP (C8) is considered to be the most important end product of mtFASII, which also forms the starting substrate of lipoic acid biosynthesis. Since lipoic acid is the cofactor of important mitochondrial enzyme complexes, such as the pyruvate dehydrogenase complex (PDC), α-ketoglutarate dehydrogenase complex (OGDC), branched-chain α-ketoacid dehydrogenase complex (BCKDC), and in

3808-423: The matrix via the citric acid cycle and in the cytoplasm by glycolysis . Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or fed into the electron transport chain using a glycerol phosphate shuttle . The major energy-releasing reactions that make the mitochondrion the "powerhouse of the cell" occur at protein complexes I, III and IV in

3876-474: The membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. Ca influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating

3944-479: The mitochondria and may contribute to the decline in mitochondrial function associated with aging. 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 (P i ). This process

4012-542: The mitochondria. And that it is mitochondria that determine lifespan. He published his ideas on what he called the " mitochondrial theory of aging " in the April 1972 issue of the Journal of the American Geriatrics Society. In 1969 Harman became concerned that few of those involved in gerontology were studying the biological aspects of aging , and fewer still had a serious interest in discovering

4080-409: The outer membrane are small (diameter: 60 Å) particles named sub-units of Parson. The mitochondrial intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in

4148-478: The outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to cell death. The outer mitochondrial membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. Outside

SECTION 60

#1732790750701

4216-402: The rate of ATP production by the mitochondrion, and thus the availability of ATP to the cell. Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids , is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and

4284-455: The reactions are controlled by an electron transport chain, free electrons are not amongst the reactants or products in the three reactions shown and therefore do not affect the free energy released, which 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

4352-459: The same pattern-recognition receptors (PRRs) that respond to pathogen-associated molecular patterns (PAMPs) during infections. For example, mitochondrial mtDNA resembles bacterial DNA due to its lack of CpG methylation and can be detected by Toll-like receptor 9 and cGAS . Double-stranded RNA (dsRNA), produced due to bidirectional mitochondrial transcription, can activate viral sensing pathways through RIG-I-like receptors . Additionally,

4420-458: The specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division. Programmed cell death (PCD) is crucial for various physiological functions, including organ development and cellular homeostasis. It serves as an intrinsic mechanism to prevent malignant transformation and plays

4488-409: The tissue's energy needs (e.g., in muscle ) are suddenly increased by activity. In the citric acid cycle, all the intermediates (e.g. citrate , iso-citrate , alpha-ketoglutarate , succinate, fumarate , malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within

4556-413: Was granted 35 patents , one for a compound used in plastic strips to kill flies ("Shell No Pest Strip"). Harman became fascinated with the phenomenon of aging , its cause and possible cure. To assist him in understanding this problem, he went to medical school at Stanford University. Harman became chair of cardiovascular research at the University of Nebraska College of Medicine in 1958. Harman

4624-509: Was married to the same woman for most of his life, a journalism student whom he met at a fraternity dance while at the University of California. The couple had four children and four grandchildren. Harman maintained a healthy lifestyle throughout his life. He never smoked and drank alcohol in moderation. He ran two miles a day until he was 82. He quit because of a back injury, but he continued to take regular walks to help him maintain

#700299