The School of Biomedical Sciences Wiki - User contributions [en]

Mitochondria

2018-12-10T00:33:54Z

170750295:

=== [[Image:Picture1.png]] ===

[[Image:Mitochondrian.PNG|right|190x187px|A cross-section of a mitochondrion under an electron microscope]]

Mitochondria (singular- Mitochondrion) are [[Membrane|membrane]] bound [[Organelles|organelles]] (double membrane structure) that can be found in animal and plant cells, that carry out [[Oxidative phosphorylation|oxidative phosphorylation]], to produce [[ATP|ATP]]. What is more, mitochondria produce the majority of [[ATP|ATP]] used by [[Eukaryotic|eukaryotic]] [[Organism|organisms]] and are often referred to as the powerhouses of the [[Cell|cell]]. Furthermore, due to the fact that mitochondria are the site [[ATP synthesis|ATP synthesis]], there is often a linear relationship between the number of mitochondria in a [[Cell|cell]] and the cells [[ATP|ATP]] requirements e.g. a [[Muscle|muscle]] cell uses vast amounts of [[ATP|ATP]] and thus often contains many mitochondria to adhere to this requirement and maintain function. A further point that must be brought to attention is that mitochondria contain their own [[DNA|DNA]] (mostly circular), referred to as [[MDNA|mtDNA]]. The size of mitochondrial [[DNA|DNA]] and its percentage of total cellular DNA varies between [[Species|species]]. In mammalian cells, only about 1% of the total cellular DNA is composed of mitochondrial DNA whereas in other organisms (for example in the egg cells of amphibians) there is a much higher percentage of mitochondrial DNA. Human [[MDNA|mitochondrial DNA]] consists of 16,569 [[Base|base]] pairs coding for 13 [[Proteins|prote]][[Proteins|ins]]. In humans, mitochondrial DNA is inherited from the mother because an egg cell has many more mitochondria than a [[Sperm cell|sperm cell]]. Mitochondria are semiautonomous [[Organelles|organelles]], depending on the host cell for their existence<ref>Berg J.M, Tymoczko J.L., Stryer L (2001) Biochemistry, 5th edition, New York: WH Freeman. p492</ref><ref>Molecular Biology of THE CELL, Fifth Edition, Alberts, Johnson, Lewis, Raff, Roberts, Watter (2008), Chapter 1 Cells and Genomes, Figure 1-33 A mitochondrion, Page 28</ref>. The outer membrane of the mitochondria contains porins which are small protein membrane channels which are permeable to most small molecules so molecules which are 10 kDa or smaller can diffuse through.

[[Image:Atp.gif|right|375px|Diagram of ATP]]ATP is hydrolysed to ADP and inorganic phosphate (Pi) in mitochondria. This process is essential to provide the 'energy currency' of cells and is maximised by the mitochondria's specialised structure.

=== Structure ===

Mitochondria:

*Range from 0.5-1μm in diameter (similar to bacteria).
*Contain an inner (folds in) and outer [[Cell membranes|membrane]].
*Contain cristae (singular crista) - internal compartments formed by the inner membrane folds. [[Image:Mitochondira.jpg|thumb|right]]
*Contain a [[Matrix|matrix]]- large overall internal compartment.[[Image:Mitochondira.jpg|thumb|right

In [[Sexual reproduction|sexual reproduction]] only the female [[Gamete|gamete]] ([[Ovum|ovum]]) has mitochondria when the gametes eventually fertilise, this is because the male gamete (sperm) draws upon all of its mitochondria for locomotion, to aid its travel to the ovum (egg). Furthermore, mitochondria in relation to the structure of the [[Sperm|sperm]] is wrapped tightly around the [[Flagellum|flagellum]] in the sperm and is fixed in this position, to enable the mitochondria to comply with the sperm's unusually high [[ATP|ATP]] consumption<ref>Bruce Alberts (et al)-2007: pg815</ref>.

The mitochondrion is the site of the [[Krebs cycle|Krebs cycle]] and the [[Electron transport chain|electron transport chain]] in [[Eukaryotic|eukaryotic]] organisms. It has a variable diameter from 0.5 to 1 micrometer thus can be easily seen under a [[Light microscope|light microscope]]. Using time-lapse micro-cinematography, it has been established that mitochondria can alter their shape continuously, and are also able to fuse and separate with other mitochondria<ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth edition, p815</ref>. It is surrounded by two [[Phospholipid membrane|phospholipid membranes]]: the outer and inner membrane. The inner membrane is folded inwards to form cristae and it is the location where  the [[Electron transport chain|electron transport chain]] occur. On the other hand, the outer membrane is the envelope that holds all the [[Organelles|organelles]] and it is relatively permeable to small molecules.

The internal mitochondrial compartment is called the [[Mitochondrial matrix|matrix]] where the link reaction and [[Krebs cycle|Krebs cycle]] occur. As a result of [[Oxidative phosphorylation|oxidative phosphorylation]], [[ATP|ATP]] is synthesised in the latter by the activity of [[ATP synthase|ATP synthase]] on the cristae. The advantage that this has over [[Glycolysis|glycolysis]] is that it reaps 15 times more ATP for all energy-requiring reactions of the cell, both inside and outside the mitochondria. Moreover, it has its own [[DNA|DNA]] which is circular and also contains 70S [[Ribosomes|ribosomes]]. In addition, it is also beneficial in the event of cell damage, as it is the one who signals the process of [[Apoptosis|apoptosis]] (programmed cell death) by releasing mitochondrial protein into the [[Cytoplasm|cytoplasm]]<ref>Berg J.M, Tymoczko J.L, Stryer (2012) Biochemistry, Seventh Edition, New York: WH Freema.. pg 543</ref><ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth Edition, pg 815</ref>.

=== Mitochondrial diseases ===

Mitochondria are the only cells apart from chloroplasts, that contain there own DNA ([[MDNA|mtDNA]]), as well as nuclear DNA<ref name="Molecular Biology of the Cell">B Alberts, A Johnson, J Lewis, D Morgan, M Raff, K Roberts, P Walter. Molecular Biology of the cell. Sixth Edition. Printed in the United States of America. Garland Science. 2015. Chapter 14.</ref>. They are susceptible to [[Mutations|mutations]] in their mtDNA base sequences because they have fewer repair mechanisms than the nuclear genome and lack [[Histones|histone]] proteins. This can lead to disease (when the [[Mutations|mutations]] are non-silent). Mutations of the mtDNA are genetically passed from generation to generation via maternal inheritance <ref>NCBI. P F. Chinnery. Gene Reviews. Mitochondrial Disorders Overview. June 8, 2000. Last update: August 14, 2014. 19/11/2016.https://www.ncbi.nlm.nih.gov/books/NBK1224/</ref>. These mutations causing gene abnormalities can give rise to a host of diseases, some of which can be fatal, and which can vary in severity from person to person<ref>The Muscular Dystrophy Association (MDA). Mitochondrial Myopathies (MM). 2016 [cited 18/11/16]; Available from: https://mda.org/disease/mitochondrial-myopathies/causes-inheritance</ref><ref>Mitochondrial Disease (MD, Mitochondrial Myopathies (MM) MedicineNet, 2016, [cited 04/12/2016] http://www.medicinenet.com/mitochondrial_disease/article.htm</ref>.

A type of [[Cardiovascular system|Cardiovascular disease]] which is associated with gene abnormalities in mtDNA and/or [[DNA|nulcear DNA]] (which encode some of the mitochondrial proteins) is Familial Dilated Cardiomyopathy<ref>U.S National Library of Medicine Genetics Home Reference. Familial Dilated Cardiomyopathy. 2016 [cited 14/11/16]; Available from: https://ghr.nih.gov/condition/familial-dilated-cardiomyopathy#genes</ref>. This disease is caused as the result of lack of [[Metabolite|metabolite]] passage across the [[Inner mitochondrial membrane|inner membrane space]]<ref>Marin-Garcia J, Goldenthal MJ. Mitochondria and the Heart. New York: Springer. 2005</ref>, due to a [[Mutations|non-silent mutation]] which results in the transport proteins having a changed genomic sequence.

Another disease, which more recently is being linked to gene abnormalities in mitochondria is [[Alzheimer's disease|Alzheimer's disease]] (AD). Free radicals are able to accumulate in the brain as a person ages, due to increased [[Oxidative phosphorylation|oxidative phosphorolation]]. The free radicals created can damage [[MDNA|mtDNA]] to cause healthy [[Neurone|neurones]] (in neuronal pathways) to become impaired which leads to a reduction in energy in the [[Neurone|neurones]]. This leads to the requirement for more [[ATP|ATP]] which comes from increased [[Oxidative phosphorylation|oxidative phosphorolation]] by unaffected/mutant mitochondria. These mitochondria with increased [[Oxidative phosphorylation|oxidative phosphorolation]] then have a selective advantage and accumulate more rapidly to cause the death of healthy [[Neurone|neurones]]<ref>Resell P. A new understanding of Alzheimer's. Harvard Gazette. 2015 February 25th.</ref>. This cascade of events continues and can eventually lead to the progression of [[Alzheimer's disease|AD]].

mtDNA also plays a key role in carcinogenesis.

=== '''mtDNA structure''' ===

mtDNA is composed of 16 regions:15 coding and one non-coding, without introns. The non-coding region of mtDNA genome is called D-loop region and is 1124 bp in size. Since D-loop region is a hot spot for different mutations such as insertion, deletion, point mutation, it may play a major role in the developing of a great number of cancerous diseases such as gastric tumours, breast cancer, ovarian carcinomas, prostatic cancer, lung and head cancer etc.

=== References ===

<references />

Mitochondria

2018-12-10T00:31:02Z

170750295:

[[Image:Picture1.png]]

[[Image:Mitochondrian.PNG|right|190x187px|A cross-section of a mitochondrion under an electron microscope]]Mitochondria (singular- Mitochondrion) are [[Membrane|membrane]] bound [[Organelles|organelles]] (double membrane structure) that can be found in animal and plant cells, that carry out [[Oxidative phosphorylation|oxidative phosphorylation]], to produce [[ATP|ATP]]. What is more, mitochondria produce the majority of [[ATP|ATP]] used by [[Eukaryotic|eukaryotic]] [[Organism|organisms]] and are often referred to as the powerhouses of the [[Cell|cell]]. Furthermore, due to the fact that mitochondria are the site [[ATP synthesis|ATP synthesis]], there is often a linear relationship between the number of mitochondria in a [[Cell|cell]] and the cells [[ATP|ATP]] requirements e.g. a [[Muscle|muscle]] cell uses vast amounts of [[ATP|ATP]] and thus often contains many mitochondria to adhere to this requirement and maintain function. A further point that must be brought to attention is that mitochondria contain their own [[DNA|DNA]] (mostly circular), referred to as [[MDNA|mtDNA]]. The size of mitochondrial [[DNA|DNA]] and its percentage of total cellular DNA varies between [[Species|species]]. In mammalian cells, only about 1% of the total cellular DNA is composed of mitochondrial DNA whereas in other organisms (for example in the egg cells of amphibians) there is a much higher percentage of mitochondrial DNA. Human [[MDNA|mitochondrial DNA]] consists of 16,569 [[Base|base]] pairs coding for 13 [[Proteins|prote]][[Proteins|ins]]. In humans, mitochondrial DNA is inherited from the mother because an egg cell has many more mitochondria than a [[Sperm cell|sperm cell]]. Mitochondria are semiautonomous [[Organelles|organelles]], depending on the host cell for their existence<ref>Berg J.M, Tymoczko J.L., Stryer L (2001) Biochemistry, 5th edition, New York: WH Freeman. p492</ref><ref>Molecular Biology of THE CELL, Fifth Edition, Alberts, Johnson, Lewis, Raff, Roberts, Watter (2008), Chapter 1 Cells and Genomes, Figure 1-33 A mitochondrion, Page 28</ref>. The outer membrane of the mitochondria contains porins which are small protein membrane channels which are permeable to most small molecules so molecules which are 10 kDa or smaller can diffuse through.

[[Image:Atp.gif|right|375px|Diagram of ATP]]ATP is hydrolysed to ADP and inorganic phosphate (Pi) in mitochondria. This process is essential to provide the 'energy currency' of cells and is maximised by the mitochondria's specialised structure.

=== Structure ===

Mitochondria:

*Range from 0.5-1μm in diameter (similar to bacteria).
*Contain an inner (folds in) and outer [[Cell membranes|membrane]].
*Contain cristae (singular crista) - internal compartments formed by the inner membrane folds. [[Image:Mitochondira.jpg|thumb|right|Mitochondira.jpg]]
*Contain a [[Matrix|matrix]]- large overall internal compartment.[[Image:Mitochondira.jpg|thumb|right

In [[Sexual reproduction|sexual reproduction]] only the female [[Gamete|gamete]] ([[Ovum|ovum]]) has mitochondria when the gametes eventually fertilise, this is because the male gamete (sperm) draws upon all of its mitochondria for locomotion, to aid its travel to the ovum (egg). Furthermore, mitochondria in relation to the structure of the [[Sperm|sperm]] is wrapped tightly around the [[Flagellum|flagellum]] in the sperm and is fixed in this position, to enable the mitochondria to comply with the sperm's unusually high [[ATP|ATP]] consumption<ref>Bruce Alberts (et al)-2007: pg815</ref>.

The mitochondrion is the site of the [[Krebs cycle|Krebs cycle]] and the [[Electron transport chain|electron transport chain]] in [[Eukaryotic|eukaryotic]] organisms. It has a variable diameter from 0.5 to 1 micrometer thus can be easily seen under a [[Light microscope|light microscope]]. Using time-lapse micro-cinematography, it has been established that mitochondria can alter their shape continuously, and are also able to fuse and separate with other mitochondria<ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth edition, p815</ref>. It is surrounded by two [[Phospholipid membrane|phospholipid membranes]]: the outer and inner membrane. The inner membrane is folded inwards to form cristae and it is the location where  the [[Electron transport chain|electron transport chain]] occur. On the other hand, the outer membrane is the envelope that holds all the [[Organelles|organelles]] and it is relatively permeable to small molecules.

The internal mitochondrial compartment is called the [[Mitochondrial matrix|matrix]] where the link reaction and [[Krebs cycle|Krebs cycle]] occur. As a result of [[Oxidative phosphorylation|oxidative phosphorylation]], [[ATP|ATP]] is synthesised in the latter by the activity of [[ATP synthase|ATP synthase]] on the cristae. The advantage that this has over [[Glycolysis|glycolysis]] is that it reaps 15 times more ATP for all energy-requiring reactions of the cell, both inside and outside the mitochondria. Moreover, it has its own [[DNA|DNA]] which is circular and also contains 70S [[Ribosomes|ribosomes]]. In addition, it is also beneficial in the event of cell damage, as it is the one who signals the process of [[Apoptosis|apoptosis]] (programmed cell death) by releasing mitochondrial protein into the [[Cytoplasm|cytoplasm]]<ref>Berg J.M, Tymoczko J.L, Stryer (2012) Biochemistry, Seventh Edition, New York: WH Freema.. pg 543</ref><ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth Edition, pg 815</ref>.

=== Mitochondrial diseases ===

Mitochondria are the only cells apart from chloroplasts, that contain there own DNA ([[MDNA|mtDNA]]), as well as nuclear DNA<ref name="Molecular Biology of the Cell">B Alberts, A Johnson, J Lewis, D Morgan, M Raff, K Roberts, P Walter. Molecular Biology of the cell. Sixth Edition. Printed in the United States of America. Garland Science. 2015. Chapter 14.</ref>. They are susceptible to [[Mutations|mutations]] in their mtDNA base sequences because they have fewer repair mechanisms than the nuclear genome and lack [[Histones|histone]] proteins. This can lead to disease (when the [[Mutations|mutations]] are non-silent). Mutations of the mtDNA are genetically passed from generation to generation via maternal inheritance <ref>NCBI. P F. Chinnery. Gene Reviews. Mitochondrial Disorders Overview. June 8, 2000. Last update: August 14, 2014. 19/11/2016.https://www.ncbi.nlm.nih.gov/books/NBK1224/</ref>. These mutations causing gene abnormalities can give rise to a host of diseases, some of which can be fatal, and which can vary in severity from person to person<ref>The Muscular Dystrophy Association (MDA). Mitochondrial Myopathies (MM). 2016 [cited 18/11/16]; Available from: https://mda.org/disease/mitochondrial-myopathies/causes-inheritance</ref><ref>Mitochondrial Disease (MD, Mitochondrial Myopathies (MM) MedicineNet, 2016, [cited 04/12/2016] http://www.medicinenet.com/mitochondrial_disease/article.htm</ref>.

A type of [[Cardiovascular system|Cardiovascular disease]] which is associated with gene abnormalities in mtDNA and/or [[DNA|nulcear DNA]] (which encode some of the mitochondrial proteins) is Familial Dilated Cardiomyopathy<ref>U.S National Library of Medicine Genetics Home Reference. Familial Dilated Cardiomyopathy. 2016 [cited 14/11/16]; Available from: https://ghr.nih.gov/condition/familial-dilated-cardiomyopathy#genes</ref>. This disease is caused as the result of lack of [[Metabolite|metabolite]] passage across the [[Inner mitochondrial membrane|inner membrane space]]<ref>Marin-Garcia J, Goldenthal MJ. Mitochondria and the Heart. New York: Springer. 2005</ref>, due to a [[Mutations|non-silent mutation]] which results in the transport proteins having a changed genomic sequence.

Another disease, which more recently is being linked to gene abnormalities in mitochondria is [[Alzheimer's disease|Alzheimer's disease]] (AD). Free radicals are able to accumulate in the brain as a person ages, due to increased [[Oxidative phosphorylation|oxidative phosphorolation]]. The free radicals created can damage [[MDNA|mtDNA]] to cause healthy [[Neurone|neurones]] (in neuronal pathways) to become impaired which leads to a reduction in energy in the [[Neurone|neurones]]. This leads to the requirement for more [[ATP|ATP]] which comes from increased [[Oxidative phosphorylation|oxidative phosphorolation]] by unaffected/mutant mitochondria. These mitochondria with increased [[Oxidative phosphorylation|oxidative phosphorolation]] then have a selective advantage and accumulate more rapidly to cause the death of healthy [[Neurone|neurones]]<ref>Resell P. A new understanding of Alzheimer's. Harvard Gazette. 2015 February 25th.</ref>. This cascade of events continues and can eventually lead to the progression of [[Alzheimer's disease|AD]].

=== '''mtDNA structure''' ===

mtDNA is composed of 16 regions:15 coding and one non-coding, without introns. The non-coding region of mtDNA genome is called D-loop region and is 1124 bp in size. Since D-loop region is a hot spot for different mutations such as insertion, deletion, point mutation, it may play a major role in the developing of a great number of cancerous diseases such as gastric tumours, breast cancer, ovarian carcinomas, prostatic cancer, lung and head cancer etc

=== References ===

<references />

File:Picture1.png

2018-12-10T00:27:29Z

170750295:

== ==

File:Picture1.png

2018-12-10T00:26:09Z

170750295: uploaded a new version of "File:Picture1.png": mtDNA

Mitochondria

2018-12-10T00:22:10Z

170750295:

[[Image:Mitochondrian.PNG|right|190x187px|A cross-section of a mitochondrion under an electron microscope]]Mitochondria (singular- Mitochondrion) are [[Membrane|membrane]] bound [[Organelles|organelles]] (double membrane structure) that can be found in animal and plant cells, that carry out [[Oxidative phosphorylation|oxidative phosphorylation]], to produce [[ATP|ATP]]. What is more, mitochondria produce the majority of [[ATP|ATP]] used by [[Eukaryotic|eukaryotic]] [[Organism|organisms]] and are often referred to as the powerhouses of the [[Cell|cell]]. Furthermore, due to the fact that mitochondria are the site [[ATP synthesis|ATP synthesis]], there is often a linear relationship between the number of mitochondria in a [[Cell|cell]] and the cells [[ATP|ATP]] requirements e.g. a [[Muscle|muscle]] cell uses vast amounts of [[ATP|ATP]] and thus often contains many mitochondria to adhere to this requirement and maintain function. A further point that must be brought to attention is that mitochondria contain their own [[DNA|DNA]] (mostly circular), referred to as [[MDNA|mtDNA]]. The size of mitochondrial [[DNA|DNA]] and its percentage of total cellular DNA varies between [[Species|species]]. In mammalian cells, only about 1% of the total cellular DNA is composed of mitochondrial DNA whereas in other organisms (for example in the egg cells of amphibians) there is a much higher percentage of mitochondrial DNA. Human [[MDNA|mitochondrial DNA]] consists of 16,569 [[Base|base]] pairs coding for 13 [[Proteins|prote]][[Proteins|ins]]. In humans, mitochondrial DNA is inherited from the mother because an egg cell has many more mitochondria than a [[Sperm cell|sperm cell]]. Mitochondria are semiautonomous [[Organelles|organelles]], depending on the host cell for their existence<ref>Berg J.M, Tymoczko J.L., Stryer L (2001) Biochemistry, 5th edition, New York: WH Freeman. p492</ref><ref>Molecular Biology of THE CELL, Fifth Edition, Alberts, Johnson, Lewis, Raff, Roberts, Watter (2008), Chapter 1 Cells and Genomes, Figure 1-33 A mitochondrion, Page 28</ref>. The outer membrane of the mitochondria contains porins which are small protein membrane channels which are permeable to most small molecules so molecules which are 10 kDa or smaller can diffuse through.

[[Image:Atp.gif|right|375px|Diagram of ATP]]ATP is hydrolysed to ADP and inorganic phosphate (Pi) in mitochondria. This process is essential to provide the 'energy currency' of cells and is maximised by the mitochondria's specialised structure.

=== Structure ===

Mitochondria:

*Range from 0.5-1μm in diameter (similar to bacteria).
*Contain an inner (folds in) and outer [[Cell membranes|membrane]].
*Contain cristae (singular crista) - internal compartments formed by the inner membrane folds. [[Image:Mitochondira.jpg|thumb|right]]
*Contain a [[Matrix|matrix]]- large overall internal compartment.[[Image:Mitochondira.jpg|thumb|right

In [[Sexual reproduction|sexual reproduction]] only the female [[Gamete|gamete]] ([[Ovum|ovum]]) has mitochondria when the gametes eventually fertilise, this is because the male gamete (sperm) draws upon all of its mitochondria for locomotion, to aid its travel to the ovum (egg). Furthermore, mitochondria in relation to the structure of the [[Sperm|sperm]] is wrapped tightly around the [[Flagellum|flagellum]] in the sperm and is fixed in this position, to enable the mitochondria to comply with the sperm's unusually high [[ATP|ATP]] consumption<ref>Bruce Alberts (et al)-2007: pg815</ref>.

The mitochondrion is the site of the [[Krebs cycle|Krebs cycle]] and the [[Electron transport chain|electron transport chain]] in [[Eukaryotic|eukaryotic]] organisms. It has a variable diameter from 0.5 to 1 micrometer thus can be easily seen under a [[Light microscope|light microscope]]. Using time-lapse micro-cinematography, it has been established that mitochondria can alter their shape continuously, and are also able to fuse and separate with other mitochondria<ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth edition, p815</ref>. It is surrounded by two [[Phospholipid membrane|phospholipid membranes]]: the outer and inner membrane. The inner membrane is folded inwards to form cristae and it is the location where  the [[Electron transport chain|electron transport chain]] occur. On the other hand, the outer membrane is the envelope that holds all the [[Organelles|organelles]] and it is relatively permeable to small molecules.

The internal mitochondrial compartment is called the [[Mitochondrial matrix|matrix]] where the link reaction and [[Krebs cycle|Krebs cycle]] occur. As a result of [[Oxidative phosphorylation|oxidative phosphorylation]], [[ATP|ATP]] is synthesised in the latter by the activity of [[ATP synthase|ATP synthase]] on the cristae. The advantage that this has over [[Glycolysis|glycolysis]] is that it reaps 15 times more ATP for all energy-requiring reactions of the cell, both inside and outside the mitochondria. Moreover, it has its own [[DNA|DNA]] which is circular and also contains 70S [[Ribosomes|ribosomes]]. In addition, it is also beneficial in the event of cell damage, as it is the one who signals the process of [[Apoptosis|apoptosis]] (programmed cell death) by releasing mitochondrial protein into the [[Cytoplasm|cytoplasm]]<ref>Berg J.M, Tymoczko J.L, Stryer (2012) Biochemistry, Seventh Edition, New York: WH Freema.. pg 543</ref><ref>Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth Edition, pg 815</ref>.

=== Mitochondrial diseases ===

Mitochondria are the only cells apart from chloroplasts, that contain there own DNA ([[MDNA|mtDNA]]), as well as nuclear DNA<ref name="Molecular Biology of the Cell">B Alberts, A Johnson, J Lewis, D Morgan, M Raff, K Roberts, P Walter. Molecular Biology of the cell. Sixth Edition. Printed in the United States of America. Garland Science. 2015. Chapter 14.</ref>. They are susceptible to [[Mutations|mutations]] in their mtDNA base sequences because they have fewer repair mechanisms than the nuclear genome and lack [[Histones|histone]] proteins. This can lead to disease (when the [[Mutations|mutations]] are non-silent). Mutations of the mtDNA are genetically passed from generation to generation via maternal inheritance <ref>NCBI. P F. Chinnery. Gene Reviews. Mitochondrial Disorders Overview. June 8, 2000. Last update: August 14, 2014. 19/11/2016.https://www.ncbi.nlm.nih.gov/books/NBK1224/</ref>. These mutations causing gene abnormalities can give rise to a host of diseases, some of which can be fatal, and which can vary in severity from person to person<ref>The Muscular Dystrophy Association (MDA). Mitochondrial Myopathies (MM). 2016 [cited 18/11/16]; Available from: https://mda.org/disease/mitochondrial-myopathies/causes-inheritance</ref><ref>Mitochondrial Disease (MD, Mitochondrial Myopathies (MM) MedicineNet, 2016, [cited 04/12/2016] http://www.medicinenet.com/mitochondrial_disease/article.htm</ref>.

A type of [[Cardiovascular system|Cardiovascular disease]] which is associated with gene abnormalities in mtDNA and/or [[DNA|nulcear DNA]] (which encode some of the mitochondrial proteins) is Familial Dilated Cardiomyopathy<ref>U.S National Library of Medicine Genetics Home Reference. Familial Dilated Cardiomyopathy. 2016 [cited 14/11/16]; Available from: https://ghr.nih.gov/condition/familial-dilated-cardiomyopathy#genes</ref>. This disease is caused as the result of lack of [[Metabolite|metabolite]] passage across the [[Inner mitochondrial membrane|inner membrane space]]<ref>Marin-Garcia J, Goldenthal MJ. Mitochondria and the Heart. New York: Springer. 2005</ref>, due to a [[Mutations|non-silent mutation]] which results in the transport proteins having a changed genomic sequence.

Another disease, which more recently is being linked to gene abnormalities in mitochondria is [[Alzheimer's disease|Alzheimer's disease]] (AD). Free radicals are able to accumulate in the brain as a person ages, due to increased [[Oxidative phosphorylation|oxidative phosphorolation]]. The free radicals created can damage [[MDNA|mtDNA]] to cause healthy [[Neurone|neurones]] (in neuronal pathways) to become impaired which leads to a reduction in energy in the [[Neurone|neurones]]. This leads to the requirement for more [[ATP|ATP]] which comes from increased [[Oxidative phosphorylation|oxidative phosphorolation]] by unaffected/mutant mitochondria. These mitochondria with increased [[Oxidative phosphorylation|oxidative phosphorolation]] then have a selective advantage and accumulate more rapidly to cause the death of healthy [[Neurone|neurones]]<ref>Resell P. A new understanding of Alzheimer's. Harvard Gazette. 2015 February 25th.</ref>. This cascade of events continues and can eventually lead to the progression of [[Alzheimer's disease|AD]].

=== '''mtDNA structure''' ===

mtDNA is composed of 16 regions:15 coding and one non-coding, without introns. The non-coding region of mtDNA genome is called D-loop region and is 1124 bp in size. Since D-loop region is a hot spot for different mutations such as insertion, deletion, point mutation, it may play a major role in the developing of a great number of cancerous diseases such as gastric tumours, breast cancer, ovarian carcinomas, prostatic cancer, lung and head cancer etc

=== References ===

<references />

2018-12-09T02:53:42Z

170750295:

HCAs(Heterocyclic Amines) are carcinogenic chemial componds that accumulate in well-cooked meat at high temperatures.The chemicals are formed when amino acids and creatin react at high cooking temperatures and found in larger quantities when meat is overcooked. HCAs pose a threat developing a carcinogenic potential after being activated by cytochrome P450 1A2-mediated oxidation of the amino groupwhich is followed by acetylation or sulfation to form direct-acting reactive mutagens that attack key elements in DNA<ref>S.-W.Choi, J.B.Mason. Cancer of the colon. Encyclopedia of Food Sciences and Nutrition 2003;second edition, pages 1543-1550</ref>

= Reference =

<references />

HCAs

2018-12-09T02:53:24Z

170750295: Created page with " HCAs(Heterocyclic Amines) are carcinogenic chemial componds that accumulate in well-cooked meat at high temperatures.The chemicals are formed when amino acids and creatin r..."

P53

2018-12-09T02:17:04Z

170750295:

P53 is a [[Tumour|tumour]] suppressor [[Gene|gene]], which accumulates when [[DNA|DNA]] is damaged beyond repair or the [[Cell|cell]] becomes stressed<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, (2008) Molecular Biology of the Cell, 5th edition, New York: Garland Science p.1123</ref>. At the acidic N-terminal, there's a Trans-activation domain (TAD), Proline-rich domain followed by the DNA binding core domain. At the C-terminal are the Tetramerization domain and C-terminal regulatory domain which includes the nuclear localisation signalling domain. In a normal cell where DNA is not damaged or when the cell is not under stress, [[Mdm2|Mdm2]] binds to P53. [[Mdm2|Mdm2]] is a [[Polyubiquitin ligase|polyubiquitin ligase]] which labels P53 for degradation. Mdm2 is not the only E3 Ubiquitin ligase to target p53 for degradation as both Pirh2 and COP1 are also involved<ref>Zhen Wang, Yi Sun,(2010), Targeting p53 for Novel Anticancer Therapy, Transl Oncol, 3(1), 1-12.</ref>. However, when DNA is damaged or the cell is stressed, [[ATM|ATM]] becomes activated which [[Phosphorylation|phosporylates]] P53 preventing the binding of [[Mdm2|Mdm2]]<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, (2008) Molecular Biology of the Cell, 5th edition, New York: Garland Science p.1105</ref>. Consequently the levels of P53 increase, inducing the production of [[P21|p21]] resulting in the inhibition [[Cdk-Cyclin|Cdk-Cyclin]] complexes which arrest the [[Cell cycle|cell division cycle]]<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, (2008) Molecular Biology of the Cell, 5th edition, New York: Garland Science p.1105-1107</ref>. When P53 level increases to a high level due to extensive DNA damage, the cell will undergo [[Apoptosis|apoptosis]].

Cancer occurs due to the loss of P53 and thus, allows the [[Cell division cycle|cell division cycle]] to progress even though DNA is damaged<ref>Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, (2008) Molecular Biology of the Cell, 5th edition, New York: Garland Science p.1106</ref>. P53 has also been recognised to be effective in the treatment of cancers, neurodegeneration, ischemia, cholestasis and atherosclerosis; this is proven by the fact that defective P53 gene contributes to the diseases. Treatment involves activating P53 gene for [[Tumour|tumour]] treatment<ref>Amaral JD, Xavier JM, Steer CJ, Rodrigues CM, 2010, Targeting the p53 pathway of apoptosis, Curr Pharm Des, 16(22), 2493-503.</ref>.

There is a number of metals that are highly toxic to p53 activity such as cadmium, aluminium, mercury and lead. Also, the imbalance between copper and zinc concentration, when the fist one is in high concentration and the latter one in low, can cause p53 gene becoming unfolded and inactivated. P53 gene is damaged when exposed to environmental factors and toxins such as: herbicides, [[pesticides|pesticides]], chlorine, [[fluoride|fluoride ]]and radiation. Moreover, p53 gene can lose its proper functioning as a result of unhealthy dietary habits. Trans fats, [[acrylamide|acrylamide]] and [[HCAs|HCAs]] found in fried food can play a great role in DNA damage(1).

 

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