Mitochondria have full cellular function as they are responsible for energy production in eukaryotic organisms, including phospholipid and heme synthesis, calcium homeostasis, apoptotic process activation, and cell death.
Changes in mitochondrial function are often associated with diseases including endocrine disruptions such as diabetes mellitus, reflecting energy homeostasis in â-cell physiology. Mitochondria retain their own genome, also reflecting bacterial evolutionary origins.
Mitochondrial biogenesis requires coordination of the nuclear and mitochondrial encoded genes in order to ensure the proper assembly and operation of a large array of proteins including the mitochondrial respiratory chain.
MitDNA defects lead to a range of diseases including Leigh's syndrome, Leber's hereditary optic neuropathy, MELAS (Lactic Oxidative Mitochondrial Encephalomyopathy and Stroke Episodes) and MERFF (Myoclonus Epilepsy with Reddish Red Fibers). Diseases resulting from mutations of mtDNA are not followed by inherited via the parental line and are of varying severity.
In most of these diseases the higher mutational burden is associated with more serious manifestations of the disease. These disorders tend to cause tissue pathology that is dependent on the absolute function of mitochondria and in particular on oxidative phosphorylation and on the minimal ability to increase glycolysis increases, suggesting a direct correlation between efficient energy production and mitochondrial mode.
Mitochondria house the main enzyme systems used to complete the oxidation of sugars, fats and proteins to produce energy in the form of ATP. Each of these three substrates can be catalysed into acetyl-CoA, which then enters the first of these processes which is the citric acid cycle, taking place in the mitochondrial region. The sugars enter the mitochondria as pyruvate after they have been glycosylated in the cytosol. Pyruvate dehydrogenase facilitates its conversion to acetyl-CáA. Beta oxidation converts fatty acids into acetyl-CoA into the mitochondria, while there are several enzymes to convert specific amino acids to pyruvate, acetyl-CoA or directly to certain citric acid cycle intermediates.
Mitochondria are in constant communication with cytosol to coordinate the balance between energy requirements and cellular and energy production with oxidative phosphorylation. This is mainly done by signaling the calcium between the cytosol and the uterus. Calcium cell signaling is of fundamental importance for most forms of activating cell states where Ca2 + signals govern most processes associated with increased energy requirements; secretion, constriction, motility, electrical stimulation where all require increased energy delivery and are usually associated with an increase in calcium cytosolic and its concentration.
Mitochondrial morphology appears to affect the bioenergy status, while changes in bioenergy often result in changes in morphology. The mitochondrial pattern is largely determined by the balance between cleavage and fusion, and this balance maintains stable state of mitochondrial morphology, mtDNA and metabolic mixing, bioenergy functionality and number of organisms. The importance of dementia and fusion homology has been highlighted by a number of diseases associated with mutations involving protein modulation, so that an imbalance leads to a shift in the morphology and viability of the organelle.
Aspects of mitochondrial biology predominantly determine irreversible cell damage in many models of cell injury or disease. Cell death is widely classified as apoptotic or necrotic - programmed or random, although the boundaries between cell death patterns are not always so clearly defined.
Apoptotic cell death plays a critical role in early development and later in life, in the removal of cells that are destroyed without the loss of energy associated with necrotic cell death. Apoptosis is an energy-dependent, active and coordinated process, while necrosis is usually the result of a metabolic failure that leads to energy collapse, breakdown of ion gradients, cell swelling, and structural disruption.
Mitochondria are at the heart of cell viability and the alterations in their function are often at the expense of the cell / organism. Mitochondria have evolved to control a variety of processes including cellular energy production, calcium signaling and apoptosis. Under aerobic conditions, mitochondria produce energy in the form of ATP and maintain an electrochemical membrane gradient. Reducing proton pumping in the membrane can lead to decreased cell viability and induction of the internal apoptotic pathway. Cytochrome c released by mitochondria is the point of no return in terms of cell survival, as this activates the activation of apoptosis.
Mechanisms are regulated by numerous proteins associated with disease states when mutations occur, highlighting the importance of organellation morphology. It is very important to understand the multifactorial role of mitochondrial function in cell viability, diseases and hereditary.
Osellame, L. D.et al. 2012. Cellular and molecular mechanisms of mitochondrial function. Best practice & research Clinical endocrinology & metabolism, 26(6), 711-723.
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