Psychology Wiki

Mitochondrial genetics

34,192pages on
this wiki






Understanding the genetic mutations that affect mitochondria can help us to understand the inner workings of cells and organisms, as well as helping to suggest methods for successful therapeutic tissue and organ cloning, and to treatments or possibly cures for many devastating muscular disorders.

Mitochondrial function and genomeEdit

Because they provide 36 molecules of ATP per glucose molecule in contrast to the 2 ATP molecules produced by glycolysis, mitochondria are essential to all higher organisms for sustaining life. The mitochondrial diseases are genetic disorders carried specifically in mitochondrial DNA; slight problems with any one of the numerous enzymes used by the mitochondria can be devastating to the cell, and in turn, to the organism.

Membrane complexes Edit

The processes carried out by the electron transport chain are mediated by protein complexes (named Complexes I-V, DHO-QO, ETF-QO, and ANT). Complex I, or NADH dehydrogenase:ubiquinone oxidoreductase, uses the energy in NADH and uses to pump protons into the intermembrane space of the mitochondrion, pumping 4 protons per electron and passing energy on to complex III (coenzyme Q or ubiquinone:Cytochrome bc1 oxidoreductase) in the form of an electron. Complex II (succinate:CoQ Oxidoreductase) accepts energy from FADH2 produced in the citric acid cycle and passes it to complex III. Complex III pumps 4 protons per electron and passes electrons to complex IV. Complex IV only pumps 2 protons into the space between the mitochondrion’s two membranes before passing the electron to O2 which reacts to form water. Complex V (ATP synthase:Proton Translocase) is a rotary complex which allows approximately (determining the actual number is very difficult) 10 protons to enter the mitochondrial matrix along their concentration gradients. It uses the energy from the gradient to form the bond between ADP and the phosphate group to create ATP. The electron transfer flavoprotein:CoQ Oxidoreductase complex is also an electron-transporting molecule and is involved in the breakdown of fatty acids and amino acids. ANT (adenine nucleotide translocator) is also involved in oxidative phosphorylation as an energy carrying molecule. Each of these eight complexes plays a vital role in the health of the cell and any slight mutation in any one of the proteins that make up these complexes can lead to cell death or stress, which can both in turn lead to a number of diseases.


Further information: Mitochondrial DNA




Genetic code variants Edit

The genetic code is, for the most part, universal, with few exceptions: mitochondrial genetics includes some of these. For most organisms the "stop codons" are “UAA”, “UAG”, and “UGA”. In vertebrate mitochondria “AGA” and “AGG” are also stop codons, but not “UGA”, which codes for tryptophan instead. “AUA” codes for isoleucine in most organisms but for methionine in vertebrate mitochondrial mRNA/tRNA.



Inheritance patternsEdit


Replication, Repair, Transcription, and Translation Edit

Mitochondrial replication is controlled by chromosomes in the nucleus and is specifically suited to make as many mitochondria as that particular cell needs at the time. Human mitochondria have three promoters, H1, H2, and L (heavy strand 1, heavy strand 2, and light strand promoters). The H1 promoter transcribes the entire heavy strand and the L promoter transcribes the entire light strand. The H2 strand causes the transcription of the two mitochondrial rRNA molecules. When transcription takes place on the heavy strand a polycistronic transcript is created. The light strand produces either small transcripts, which can be used as primers, or one long transcript. The transcripts are then cut into functional tRNA, rRNA, and mRNA molecules. Mitochondrial translation is still not very well understood. In vitro translations have still not been successful, probably due to the difficulty of isolating sufficient mt mRNA, functional mt rRNA, and possibly because of the complicated changes that the mRNA undergoes before it is translated.


Mitochondrial polymerase is used in the copying of mtDNA during replication. Because the two (heavy and light) strands on the circular mtDNA molecule have different origins of replication, it replicates in a D-loop (displacement) configuration. One strand begins to replicate first, displacing the other strand. This continues until replication reaches the origin of replication on the other strand, at which point the other strand beings replicating in the opposite direction. This results in two new mtDNA molecules. Each mitochondria has several copies of the mtDNA molecule and the number of mtDNA molecules is a limiting factor in mitochondrial fission. After the mitochondrion has enough mtDNA, membrane area, and membrane proteins, it can undergo fission (very similar to that which bacteria use) to become two mitochondria. Evidence suggests that mitochondria can also undergo fusion and exchange (in a form of crossover) genetic material among each other. Mitochondria sometimes form large matrices in which fusion, fission, and protein exchanges are constantly occurring. mtDNA shared among mitochondria (despite the fact that they can undergo fusion).

Damage and transcription errorEdit

Mitochondrial DNA is prone to damage from free oxygen radicals from mistakes that occur during the production of ATP through the electron transport chain. These mistakes can be caused by genetic disorders, cancer, and temperature variations. These radicals can damage mtDNA molecules or change them, making it hard for mitochondrial polymerase to replicate them. Both cases can lead to deletions, rearrangements, and other mutations. Recent evidence has suggested that mitochondria have enzymes that proofread mtDNA and fix mutations that may occur due to free radicals. It is believed that a DNA recombinase found in mammalian cells is also involved in a repairing recombination process. Deletions and mutations due to free radicals have been associated with the aging process. It is believed that radicals cause mutations which lead to mutant proteins, which in turn lead to more radicals. This process takes many years and is associated with some aging processes involved in oxygen-dependent tissues such as brain, heart, muscle, and kidney. Auto-enhancing processes such as these are possible causes of degenerative diseases including Parkinson’s, Alzheimer’s, and coronary artery disease.

Chromosomally Mediated mtDNA Replication Errors Edit

Because mitochondrial growth and fission are mediated by the nuclear DNA, mutations in nuclear DNA can have a wide array of effects on mtDNA replication. Despite the fact that the loci for some of these mutations have been found on human chromosomes, specific genes and proteins involved have not yet been isolated. Mitochondria need a certain protein to undergo fission. If this protein (made by the nucleus) is not present, the mitochondria grow but they do not divide. This leads to giant, inefficient mitochondria. Mistakes in chromosomal genes or their products can also affect mitochondrial replication more directly by inhibiting mitochondrial polymerase and can even cause mutations in the mtDNA directly and indirectly. Indirect mutations are most often caused by radicals created by defective proteins made from nuclear DNA.

Mitochondrial Diseases Edit

Mitochondrial diseases range in severity from almost not diagnosable to fatal. They also range in cause from inherited to acquired mutations (although acquired mutations that cause disease are very rare). A certain mutation can cause several different diseases depending on the severity of the problem in the mitochondria and the tissue the affected mitochondria are in. Conversely, several different mutations may present themselves as the same disease. This almost patient-specific characterization of mitochondrial diseases makes them very hard to accurately diagnose and trace. Some diseases are observable at or even before birth (most causing death) while others do not show themselves until late adulthood. This is because the number of mutant versus wildtype mitochondria varies from cell to cell and tissue to tissue, and is always changing. Because cells have multiple mitochondria, different mitochondria in the same cell can have different variations of the mtDNA genome. This condition is referred to as heteroplasmy. When a certain tissue reaches a certain ration of mutant versus wildtype mitochondria, a disease will present itself. The ration varies from person to person and tissue to tissue (depending on its specific energy, oxygen, and metabolism requirements, and the effects of the specific mutation). Mitochondrial diseases are very numerous and different. Apart from diseases definitely caused by abnormalities in mitochondrial DNA, many diseases are suspected to be caused in part by dysfunction of mitochondria, such as diabetes mellitus, forms of cancer and cardiovascular disease, lactic acidosis, specific forms of myopathy, osteoporosis, Alzheimer's disease, Parkinsons's disease, stroke, and many more. Furthermore, mtDNA mutations are believed to play a role in the aging process.

Notes Edit

  1. ^  Societat Catalana de Neurologia. URL accessed on December 5, 2005.
  2. ^ URL accessed on December 5, 2005.

See also Edit

Sources Edit

  1. Roberts D, Frerman F, and Kim J. (Dec. 1996) Three-dimensional Structure of Human Electron Transfer Flavoprotein to 2.1-Å Resolution. Proc. Natl. Acad. Sci. USA. Vol. 93. (dl Nov. 2004).
  2. Naviaux, Robert. (1997) The Spectrum of Mitochondrial Disease. Exceptional Parent Magazine. Vol. 27, Issue 8.
  3. Crofts, Antony R. (1996) Biophysics 354: Biological Energy Conversions. University of Illinois at Urbana-Champaign. (dl Nov. 2004).
  4. Nester, Anderson, Roberts, Pearsall, Nester. Microbiology, A Human Perspective. Boston: McGraw Hill Inc; 2004.
  5. Broughton R, Milam J, and Roe B. (Nov. 2001) The Complete Sequence of the Zebrafish (Danio rerio) Mitochondrial Genome and Evolutionary Patterns in Vertebrate Mitochondrial DNA. Genome Research. Vol. 11, Issue 11. (dl Nov. 2004).
  6. Neuromuscular Disease Center. Washington University, St. Louis, MO; October 10, 2004. (dl Nov. 2004).
  7. Montoya J, Playán A, Alcaine M, Enríquez J, Fernández-Silva P, López-Pérez M, Martinez-Azorín F, Pérez-Martos A. Societat Catalana de Neurologia. Universidad de Zaragoza. (dl Nov. 2004).
  8. United Mitochondrial Disease Foundation. St. Louis, MO. (dl Nov. 2004).
  9. Tamarin, Robert H. Principles of Genetics, Seventh Edition. New York, NY: McGraw-Hill Inc; 2002.
  10. Scheffler, Immo E. (2000) Review Article: A Century of Mitochondrial Research: Achievements and Perspectives. Elsevier Science B. V. and Mitochondrial Research Society. (dl Nov. 2004).
  11. Vladutiu, Georgirene D. (1997) Advances in Mitochondrial Disease Research. Exceptional Parent Magazine. Vol. 27, Issue 8.
  12. DiMauro, Salvatore. (1997) Promising Avenues of Investigation in the Diagnosis and Treatment of Mitochondrial Defects. Exceptional Parent Magazine. Vol. 27, Issue 8.
  13. University of Texas Medical Branch. TX; Dec. 2003. The Mitochondrial Life Cycle. (dl Nov. 2004).
  14. The Mitochondrial Research Society. Mitochondria Means the Most to US; 2004. (dl Nov. 2004).
  15. Purves W, Sadava D, Orians G, Heller C. Life: The Science of Biology, Sixth Edition. Massachusetts: Sinauer Associates, Inc;ális genetika

Around Wikia's network

Random Wiki