|Embryology - 15 Dec 2018 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Maternal Inheritance
- 4 History Mitochodria
- 5 Evolution Mitochondria
- 6 Mitochondrial Genome
- 7 Spindle Transfer
- 8 Oocyte Mitochondria
- 9 Mitochondria Components
- 10 Mitochondrial Disorders
- 11 References
- 12 Terms
- 13 External Links
- 14 Glossary Links
Originally discovered in muscle by Kölliker in 1857, mitochondria are the "powerhouses" of the cell and the location where respiration occurs at the cellular level. These cytoplasmic organelles also contain their own DNA (mitochondrial DNA or mtDNA) that has been originally inherited only from the oocyte (maternal inheritance). The spermatozoa (paternal) mitochondria, required for energy for fertilization motility, can enter the oocyte but are generally destroyed during the first mitotic cell divisions. This pattern of inheritance has important implications for a variety of mitochondrial associated diseases, usually occurring in tissues requiring lots of energy (muscle, brain) and in the pathogenesis of common late-onset disorders. Recent experiments have employed swapping maternal mitochondrial DNA in mammalian oocytes, in order to overcome mitochondrial inherited diseases, raising both scientific and ethical discussion on mitochondrial donation.
Swapping mitochondrial DNA mammalian oocytes
|Mitochondria Links: mitochondria | genetics | Assisted Reproductive Technology | genetic abnormalities | Cell Biology - Mitochondria|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Christos Chinopoulos, Spyros Batzios, Lambertus P van den Heuvel, Richard Rodenburg, Roel Smeets, Hans R Waterham, Marjolein Turkenburg, Jos P Ruiter, Ronald J A Wanders, Judit Doczi, Gergo Horvath, Arpad Dobolyi, Euthymia Vargiami, Ron A Wevers, Dimitrios Zafeiriou Mutated SUCLG1 causes mislocalization of SUCLG2 protein, morphological alterations of mitochondria and an early-onset severe neurometabolic disorder. Mol. Genet. Metab.: 2018; PubMed 30470562
Natalia V Motorna, Tatyana Yu Kvitnitskaya-Ryzhova, Svetlana L Rybalko, Daria B Starosyla, Rostyslav F Kaminsky, Serhii I Savosko, Liudmyla M Sokurenko, Yurii B Chaikovsky Experimental study of the liver ultrastructure in the presence of infection with herpes simplex virus 1. Wiad. Lek.: 2018, 71(7);1235-1241 PubMed 30448790
Agnieszka Milon, Piotr Pawlicki, Agnieszka Rak, Ewa Mlyczynska, Bartosz J Płachno, Waclaw Tworzydlo, Ewelina Gorowska-Wojtowicz, Barbara Bilinska, Malgorzata Kotula-Balak Telocytes are localized to testis of the bank vole (Myodes glareolus) and are affected by lighting conditions and G-coupled membrane estrogen receptor (GPER) signaling. Gen. Comp. Endocrinol.: 2018; PubMed 30391242
Kristen M McGreevy, Kira L Heikes, Shiri Kult, Marla E Tharp, Bob Goldstein ##Title## Cold Spring Harb Protoc: 2018, 2018(11);pdb.prot106021 PubMed 30385676
Masahito Tachibana, Takashi Kuno, Nobuo Yaegashi Mitochondrial replacement therapy and assisted reproductive technology: A paradigm shift toward treatment of genetic diseases in gametes or in early embryos. Reprod. Med. Biol.: 2018, 17(4);421-433 PubMed 30377395
- Oocyte mitochondria (maternal) are the only mitochondria inherited. (see genetics below)
- maternal mitochondrial genome inheritance.
- Spermatozoa mitochondria (paternal) can enter oocyte at fertilisation.
- Male spermatozoa are destroyed early in embryonic development (mechanism not yet elucidated)
- worm - (C. elegans) suggest ubiquitination occurs followed by autophagy.
- mouse - suggest a more passive process, prefertilization sperm mtDNA elimination and uneven mitochondrial distribution in embryos.
| Spermatozoa organelles, including mitochondria, are destroyed in some species by the process of autophagy following fertilisation.
Recent studies in mice suggest that additional mechanisms may be used in paternal mitochondrial elimination.
- Links: Spermatozoa Development
1857 Kölliker discovers mitochondria in muscle
1929 Karl Lohmann discovered ATP
1940s and 1950s ATP is formed in cell respiration in mitochondria and photosynthesis in chloroplasts of plants
1960 Efraim Racker and co-workers isolated, from mitochondria, the enzyme "F o F 1 ATPase" now call ATP synthase
1992 Wallace identified degenerative disease caused by mtDNA mutations
1997 Nobel Prize in Chemistry - The three laureates have performed pioneering work on enzymes that participate in the conversion of the "high-energy" compound adenosine triphosphate (ATP).
- Paul D. Boyer and John E. Walker "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)"
- Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase
- primitive Eubacterium
- symbiotic relationship with eukaryotic cell
- circular DNA
- see antibiotic-induced deafness due to similarity of mitochondrial and bacterial ribosomes
- genes transferred to nucleus
- mitochondrial genome bp
- 366,924 Arabidopsis
- 16,569 Human
- 5966 Plasmodium
- In humans this genome is maternally inherited.
- Exists as multiple copies within the matrix of each mitochondrion within the cytoplasm of cells.
- In 1981 the human mitochondrial genome was sequenced.
- The genome is a small circular DNA molecule 16,568 bp in length containing 37 genes.
- 24 genes specify RNA molecules involved in protein synthesis (22 transfer RNAs (tRNA) and 2 ribosomal RNAs (rRNA))
- 13 genes encode proteins required for the biochemical reactions that make up respiration.
(ST) An Assisted Reproductive Technology term referring to the transfer of the metaphase II-arrested (MII) spindle-chromosomal complex isolated as a karyoplast from a donor oocyte to the cytoplasm of a second recipient oocyte. The term cytoplast refers to the enucleated recipient oocyte. This technique has been suggested as a clinical solution to mitochondrial inherited disorders.
Swapping mitochondrial DNA mammalian oocytes
- mitochondria DNA (mtDNA) copy numbers gradually increased as folliculogenesis progressed
- significant shift at the small antral stage (0.5 to <1 mm in diameter)
- location of mitochondria gradually shifted
- pre-antral oocytes - homogeneous cytoplasm distribution throughout
- advanced antral stage - pericortical concentration in the advanced antral stage
- progressive increase in mitochondrial activity in oocytes from the pre-antral to the large antral follicles.
Another study of obesity-exposed oocytes, show that they accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. Mitophagy is a term used for the selective degradation of mitochondria by autophagy.
- porin - membrane channel, allows ions and metabolites into the mitochondria (<5000 daltons)
- similar to the cytosol with respect to the small molecules it contains
- also enzymes that use ATP
- cardiolipin - phospholipid, makes membrane impermeable to ions (unique to mitochondria inner membrane)
- transport proteins - permeable to molecules required in the matrix
- increase inner membrane surface area
- tubular, vesicular or flat cristae
- Adenosine triphosphate (ATP) synthase
- respiratory electron transfer chain proteins
- transport proteins
- metabolic enzymes of citric acid cycle (=Krebs) (100s of enzymes) (MH- do not need to know biochemical details of this cycle)
- genetic material DNA, tRNA, ribosomes
- double stranded circular DNA (mitoDNA. mtDNA)
- 1981 complete human sequence (16,569 nucleotides)
- 37 genes
- encodes 13 polypeptides involved in oxidative phosphorylation
- remaining genes transfer RNA (tRNA) and ribosomal RNA (rRNA)
- multiple copies within the matrix
- maternally inherited
- remainder encoded by nuclear DNA
- proteins made in cytosol and imported into mitochondria
Mitochondria Protein Synthesis
Many mitochondrial proteins are encoded by nuclear DNA
- synthesis begins in the cell cytoplasm
- imported into the mitochondria
- targeting similar to signal sequence for RER
- once in matrix signal sequence is cleaved (by Hsp70)
- protein then folds (by Hsp60)
- proteins for mitochondrial membrane or intermembranous space
- additional signal following matrix localization
Mitochondrial targeting signal (MTS) - alternating amino acid pattern (amphipathic helix) with a few hydrophobic amino acids and a few plus-charged amino acids at the N terminus.
There has been recent discussion on the use of specialised Assisted Reproductive Technology (ART) techniques to allow replacement of maternal mitochondria with genetic abnormalities with a healthy donor mitochondria.
|Mitochondrial DNA disorder||Description||Prevalence||Life expectancy/morbidity|
|Kearns–Sayre syndrome||Progressive blindness and blocked heart||Rare disease||Onset before 15|
|Chronic progressive external opthalmoplegia (CPEO)||Progressive wastage of eyelids, eyes and sometimes facial muscles||Rare disease||Onset in young adulthood|
|Pearson syndrome||Anaemia, pancreatic failure, muscle wastage||Very rare (less than 100 worldwide)||Early death|
|Myopathy, encephalopathy, lactic acidosis and stroke (MELAS)||Stroke like episodes; muscle spasm; early dementia||Rare disease||Death before 40|
|Myoclonic epilepsy and ragged-red fibres (MERFF)||Epilepsy, hearing loss, lactic acidosis, short stature||1 in 400,000 across Europe||Childhood onset|
|Neurogenic weakness, ataxia and retinitis pigmentosa (NARP)||Muscle weakness, vision loss, learning disabilities||Rare disease||Onset in early childhood. Early death|
|Maternally inherited Leigh syndrome (MILS)||Muscle weakness, heart and kidney failure, delayed development||Very rare||Onset in infancy. Death in early childhood|
|Maternally inherited diabetes and deafness (MIDD)||Combination of all types of diabetes with deafness||Rare disease||Adult onset|
|Leber hereditary optic neuropathy (LHON)||Rapid blindness||1 in 30,000 across Europe||Range from early childhood to 70s|
|Myopathy and diabetes||Covers forms of muscular dystrophy||From infancy. Early death|
|Sensorineural hearing loss||Covers a range of hearing loss through to deafness||Common condition but rarely caused by mitochondrial disease||Onset at any age|
|Exercise intolerance||Range from lethargy to muscle wastage||1 in 8,000 but symptoms often combine with others||Onset in early life|
| Fatal infantile encephalopathy
|Brain and nervous system dysfunctions||Very rare||Onset in infancy. Death in early childhood|
|Table based on Annex D, UK Mitochondrial Donation 2014.|
- Craven L, Murphy J, Turnbull DM, Taylor RW, Gorman GS & McFarland R. (2018). Scientific and Ethical Issues in Mitochondrial Donation. New Bioeth , 24, 57-73. PMID: 29529980 DOI.
- Shoubridge EA. (2009). Developmental biology: Asexual healing. Nature , 461, 354-5. PMID: 19759608 DOI.
- Luo SM, Ge ZJ, Wang ZW, Jiang ZZ, Wang ZB, Ouyang YC, Hou Y, Schatten H & Sun QY. (2013). Unique insights into maternal mitochondrial inheritance in mice. Proc. Natl. Acad. Sci. U.S.A. , 110, 13038-43. PMID: 23878233 DOI.
- Floros VI, Pyle A, Dietmann S, Wei W, Tang WCW, Irie N, Payne B, Capalbo A, Noli L, Coxhead J, Hudson G, Crosier M, Strahl H, Khalaf Y, Saitou M, Ilic D, Surani MA & Chinnery PF. (2018). Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos. Nat. Cell Biol. , 20, 144-151. PMID: 29335530 DOI.
- Boudoures AL, Saben J, Drury A, Scheaffer S, Modi Z, Zhang W & Moley KH. (2017). Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. Dev. Biol. , 426, 126-138. PMID: 28438607 DOI.
- Samuels DC, Li C, Li B, Song Z, Torstenson E, Boyd Clay H, Rokas A, Thornton-Wells TA, Moore JH, Hughes TM, Hoffman RD, Haines JL, Murdock DG, Mortlock DP & Williams SM. (2013). Recurrent tissue-specific mtDNA mutations are common in humans. PLoS Genet. , 9, e1003929. PMID: 24244193 DOI.
- Sharpley MS, Marciniak C, Eckel-Mahan K, McManus M, Crimi M, Waymire K, Lin CS, Masubuchi S, Friend N, Koike M, Chalkia D, MacGregor G, Sassone-Corsi P & Wallace DC. (2012). Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition. Cell , 151, 333-343. PMID: 23063123 DOI.
- Hajjar C, Sampuda KM & Boyd L. (2014). Dual roles for ubiquitination in the processing of sperm organelles after fertilization. BMC Dev. Biol. , 14, 6. PMID: 24528894 DOI.
- Al Rawi S, Louvet-Vallée S, Djeddi A, Sachse M, Culetto E, Hajjar C, Boyd L, Legouis R & Galy V. (2011). Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science , 334, 1144-7. PMID: 22033522 DOI.
- Songsasen N, Henson LH, Tipkantha W, Thongkittidilok C, Henson JH, Chatdarong K & Comizzoli P. (2017). Dynamic changes in mitochondrial DNA, distribution and activity within cat oocytes during folliculogenesis. Reprod. Domest. Anim. , 52 Suppl 2, 71-76. PMID: 28111812 DOI.
Lima A, Burgstaller J, Sanchez-Nieto JM & Rodríguez TA. (2018). The Mitochondria and the Regulation of Cell Fitness During Early Mammalian Development. Curr. Top. Dev. Biol. , 128, 339-363. PMID: 29477168 DOI.
Floros VI, Pyle A, Dietmann S, Wei W, Tang WCW, Irie N, Payne B, Capalbo A, Noli L, Coxhead J, Hudson G, Crosier M, Strahl H, Khalaf Y, Saitou M, Ilic D, Surani MA & Chinnery PF. (2018). Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos. Nat. Cell Biol. , 20, 144-151. PMID: 29335530 DOI.
Boudoures AL, Saben J, Drury A, Scheaffer S, Modi Z, Zhang W & Moley KH. (2017). Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy. Dev. Biol. , 426, 126-138. PMID: 28438607 DOI.
Search Pubmed: Mitochondria
- maternal spindle transfer - (MST) An Assisted Reproductive Technology term. The “maternal spindle” is the group of maternal chromosomes within the oocyte, which are shaped in a spindle. The transfer technique involves removing the spindle from the mother’s oocyte before it is fertilised by the father’s spermatozoa. The spindle is then placed into a donor oocyte with healthy mitochondria, from which the donor’s spindle, and therefore her nuclear material, has been removed.
- Pro-nuclear transfer - (PNT) An Assisted Reproductive Technology term. The pro-nucleus is the nucleus of either a spermatozoa or an oocyte during the process of fertilisation after the sperm enters the egg, but before they fuse. Transfer involves removing the pro-nuclei from a newly fertilized oocyte that has unhealthy mitochondria. The pro-nuclei are then transferred into a donated embryo, with healthy mitochondria, that has had its own, original pro-nuclei removed.
|Cell Division Terms|
| Meiosis | Mitosis
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Cite this page: Hill, M.A. (2018, December 15) Embryology Mitochondria. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mitochondria
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