Mitochondria

Mitochondria (singular- Mitochondrion) are membrane bound organelles (double membrane structure) that can be found in animal and plant cells, that carry out oxidative phosphorylation, to produce ATP. What is more, mitochondria produce the majority of ATP used by eukaryotic organisms and are often referred to as the powerhouses of the cell. Furthermore, due to the fact that mitochondria are the site ATP synthesis, there is often a linear relationship between the number of mitochondria in a cell and the cells ATP requirements e.g. a muscle cell uses vast amounts of 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 (mostly circular), referred to as mtDNA. The size of mitochondrial DNA and its percentage of total cellular DNA varies between 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 mitochondrial DNA consists of 16,569 base pairs coding for 13 proteins. In humans, mitochondrial DNA is inherited from the mother because an egg cell has many more mitochondria than a sperm cell. Mitochondria are semiautonomous organelles, depending on the host cell for their existence^[1][2]. 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.

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.

Contents 1 Structure 2 Mitochondrial diseases 3 mtDNA structure 4 Origins 5 References

Structure

Mitochondria:

• Range from 0.5-1μm in diameter (similar to bacteria).
• Contain an inner (folds in) and outer membrane.
• Contain cristae (singular crista) - internal compartments formed by the inner membrane folds.
  

  

  Mitochondira.jpg
• Contain a matrix- large overall internal compartment.[[Image:Mitochondira.jpg|thumb|right

In sexual reproduction only the female gamete (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 is wrapped tightly around the flagellum in the sperm and is fixed in this position, to enable the mitochondria to comply with the sperm's unusually high ATP consumption^[3].

The mitochondrion is the site of the Krebs cycle and the electron transport chain in eukaryotic organisms. It has a variable diameter from 0.5 to 1 micrometer thus can be easily seen under a 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^[4]. It is surrounded by two 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 occur. On the other hand, the outer membrane is the envelope that holds all the organelles and it is relatively permeable to small molecules.

The internal mitochondrial compartment is called the matrix where the link reaction and Krebs cycle occur. As a result of oxidative phosphorylation, ATP is synthesised in the latter by the activity of ATP synthase on the cristae. The advantage that this has over 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 which is circular and also contains 70S ribosomes. In addition, it is also beneficial in the event of cell damage, as it is the one who signals the process of apoptosis (programmed cell death) by releasing mitochondrial protein into the cytoplasm^[5][6].

Mitochondrial diseases

Mitochondria are the only cells apart from chloroplasts, that contain there own DNA (mtDNA), as well as nuclear DNA^[7]. They are susceptible to mutations in their mtDNA base sequences because they have fewer repair mechanisms than the nuclear genome and lack histone proteins. This can lead to disease (when the mutations are non-silent). Mutations of the mtDNA are genetically passed from generation to generation via maternal inheritance ^[8]. 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^[9][10].

A type of Cardiovascular disease which is associated with gene abnormalities in mtDNA and/or nulcear DNA (which encode some of the mitochondrial proteins) is Familial Dilated Cardiomyopathy^[11]. This disease is caused as the result of lack of metabolite passage across the inner membrane space^[12], due to a 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 (AD). Free radicals are able to accumulate in the brain as a person ages, due to increased oxidative phosphorolation. The free radicals created can damage mtDNA to cause healthy neurones (in neuronal pathways) to become impaired which leads to a reduction in energy in the neurones. This leads to the requirement for more ATP which comes from increased oxidative phosphorolation by unaffected/mutant mitochondria. These mitochondria with increased oxidative phosphorolation then have a selective advantage and accumulate more rapidly to cause the death of healthy neurones^[13]. This cascade of events continues and can eventually lead to the progression of 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.

Origins

Whilst the exact origins of the Mitochondrion we see in Eukaryotes today are not entirely clear, and the evidence to move any hypothesis into theory is likely lost to time. However the hypothesis that seems to be the most popular is that Mitochondria are endosymbiotes, originally proto-bacteria that have been incorporated into other cells^[14]. 

References

1. ↑ Berg J.M, Tymoczko J.L., Stryer L (2001) Biochemistry, 5th edition, New York: WH Freeman. p492
2. ↑ 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
3. ↑ Bruce Alberts (et al)-2007: pg815
4. ↑ Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth edition, p815
5. ↑ Berg J.M, Tymoczko J.L, Stryer (2012) Biochemistry, Seventh Edition, New York: WH Freema.. pg 543
6. ↑ Alberts, Johnson, Lewis, Raff, Roberts, Walter (2008) Molecular Biology of the cell, Fifth Edition, pg 815
7. ↑ 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.
8. ↑ 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/
9. ↑ The Muscular Dystrophy Association (MDA). Mitochondrial Myopathies (MM). 2016 [cited 18/11/16]; Available from: https://mda.org/disease/mitochondrial-myopathies/causes-inheritance
10. ↑ Mitochondrial Disease (MD, Mitochondrial Myopathies (MM) MedicineNet, 2016, [cited 04/12/2016] http://www.medicinenet.com/mitochondrial_disease/article.htm
11. ↑ 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
12. ↑ Marin-Garcia J, Goldenthal MJ. Mitochondria and the Heart. New York: Springer. 2005
13. ↑ Resell P. A new understanding of Alzheimer's. Harvard Gazette. 2015 February 25th.
14. ↑ Woese C, Kandler O, Wheelis M. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proceedings of the National Academy of Sciences. 1990;87(12):4576-4579.