Cell Mitochondria - CellBiology · PDF fileCell Mitochondria Introduction ... Jens C. Skou...

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Cell Mitochondria Introduction This lecture introduces the cytoplasmic organelles that produce the energy required for cellular processes to occur. In recent years mitochondria have also been shown to have important roles in other cellular functions, in particular, cell death by apoptosis. This second role will be covered in detail in later lectures in this current series. (/cellbiology/index.php/File:01lungtem.jpg) (/cellbiology/index.php/File:08lungtem.jpg) Welcome to the Matrix! Mitochondrion is singular, Mitochondria is plural (/cellbiology/index.php/File:Mitochondria_fl.jpg) Labeled Mitochondria Movie (1 frame/2 seconds) (http://cellbiology.med.unsw.edu.au/units/movies/mitochondria/B35mitotag1F2sec.mov) (/cellbiology/index.php/Mitochondria_Movie_1) Mitochondria Page (/cellbiology/index.php/Mitochondria_Movie_1) | Play (/cellbiology/images/9/94/Mitochondria_movie_1.mp4) (/cellbiology/index.php/Mitoch Mitochondria Page (/cellbiology/index.php/ Play (/cellbiology/images/a/a0/Mito Lecture Archive: 2016 (https://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Cell_Mitochondria&oldid=76076) Objectives Broad understanding of processes requiring energy within the cell Brief understanding structure and function of plant chloroplast Understand the structure and function of plant and animal mitochondria Brief understanding of mitochondria evolution Brief understanding of mitochondrial abnormalities Textbooks Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Mitochondrion. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26894/ (https://www.ncbi.nlm.nih.gov/books/NBK26894/) Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Mitochondria. Available from:

Transcript of Cell Mitochondria - CellBiology · PDF fileCell Mitochondria Introduction ... Jens C. Skou...

Page 1: Cell Mitochondria - CellBiology · PDF fileCell Mitochondria Introduction ... Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase Evolution Mitochondria

Cell Mitochondria

IntroductionThis lecture introduces the cytoplasmic organelles that produce the energy required for cellular processes to occur. In recent years mitochondria have also beenshown to have important roles in other cellular functions, in particular, cell death by apoptosis. This second role will be covered in detail in later lectures in thiscurrent series.

(/cellbiology/index.php/File:01lungtem.jpg)

(/cellbiology/index.php/File:08lungtem.jpg)

Welcome to the Matrix!

Mitochondrion is singular, Mitochondria is plural

(/cellbiology/index.php/File:Mitochondria_fl.jpg)Labeled Mitochondria Movie (1 frame/2 seconds)(http://cellbiology.med.unsw.edu.au/units/movies/mitochondria/B35mitotag1F2sec.mov)

(/cellbiology/index.php/Mitochondria_Movie_1) MitochondriaPage (/cellbiology/index.php/Mitochondria_Movie_1) |Play(/cellbiology/images/9/94/Mitochondria_movie_1.mp4)

(/cellbiology/index.php/Mitochondria_Movie_2) MitochondriaPage (/cellbiology/index.php/Mitochondria_Movie_2)Play(/cellbiology/images/a/a0/Mitochondria_movie_2.mp4)

Lecture Archive: 2016 (https://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=Cell_Mitochondria&oldid=76076)

ObjectivesBroad understanding of processes requiring energy within the cellBrief understanding structure and function of plant chloroplastUnderstand the structure and function of plant and animal mitochondriaBrief understanding of mitochondria evolutionBrief understanding of mitochondrial abnormalities

TextbooksAlberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Mitochondrion. Available from:https://www.ncbi.nlm.nih.gov/books/NBK26894/ (https://www.ncbi.nlm.nih.gov/books/NBK26894/)Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Mitochondria. Available from:

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(/cellbiology/index.php/File:Mitochondrion_structure_cartoon.jpg)Mitochondrion structure cartoon

https://www.ncbi.nlm.nih.gov/books/NBK9896/ (https://www.ncbi.nlm.nih.gov/books/NBK9896/)Review - David J Pagliarini, Jared Rutter Hallmarks of a new era in mitochondrial biochemistry. Genes Dev.: 2013, 27(24);2615-27 PubMed 24352419(http://www.ncbi.nlm.nih.gov/pubmed/24352419)

Double Membrane OrganellesNucleus - all eukaryotesChloroplasts - plantsMitochondria - plants and animals

History Mitochodria1857 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 ATPsynthase

1963 There’s DNA in those organelles (http://jcb.rupress.org/cgi/content/full/168/6/853) DNA is directly visualizedin first chloroplasts and then mitochondria, from the JCB Archive(http://jcb.rupress.org/misc/fromthearchive.shtml).

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" compoundadenosine 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

Evolution Mitochondriaprimitive Eubacterium (alphaproteobacteria-like ancestor)symbiotic relationship with eukaryotic cell

circular DNAsee antibiotic-induced deafness due to similarity of mitochondrial and bacterial ribosomes

genes transferred to nucleusmitochondrial genome bp

366,924 Arabidopsis16,569 Human5966 Plasmodium

Chloroplasts

(/cellbiology/index.php/File:Plant_cell_structure.png)

Plant cell structure

(/cellbiology/index.php/File:Chloroplast1.jpg)

Plant Chloroplastorganelles

Double membrane cytoplasmic organellepresent in photosynthetic Eubacteria, algae and plants

thought to originate as an endosymbiotic cyanobacteria (blue-green algae)

Functionphotosynthesischlorophyll captures light energychloroplasts interact with peroxisomes

Structureflat discs usually 2 to 10 micrometer in diameter and 1 micrometer thick.plants 5 μm in diameter and 2.3 μm thickinner and an outer phospholipid membraneintermembranous spacestroma

stacks of thylakoids (site of photosynthesis)contains copies of small circular DNAribosomes

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(/cellbiology/index.php/File:Heart_mitochondria.jpg)Heart mitochondria

(/cellbiology/index.php/File:Mitochondrial_membraneous_compartments.jpg)Mitochondrial membraneous compartments

(/cellbiology/index.php/File:Mitochondrion_rat_liver.jpg)Mitochondrion rat liver

proteins transported to the chloroplast(MH - will not cover this cell organelle in any depth in current course)

MitochondriaGreek, mito = thread; chondrion = granuleLocated throughout cytoplasmic compartment

has itself several membrane enclosed compartmentseach compartment has different function

Ancient aerobic organisms in symbiosis (endosymbiosis)present in all cells

Mitochondria FunctionEnergy production

Respiratory chainSignalingApoptosis role

Programmed cell death

Mitochondria StructureDouble membraneouter membraneintermembrane spaceinner membranecrista (plural, cristae)

originally considered specialized folds of the inner membranevariable invaginations with narrow tubular connections to each other and by crista junctions to theperipheral region of inner membrane

matrix

Mitochondria ShapeCome in different shapes & sizesCan rapidly change shape (minutes)

(/cellbiology/index.php/File:01lungtem.jpg)

(/cellbiology/index.php/File:Cardiac_muscle_mitochondria.jpg)Lung Cardiac muscleMitochodrial Movie (http://cellbiology.med.unsw.edu.au/units/movies/mitochondria/B35mitotag1F2sec.mov)

Mitochondria Locationcells with high energy requirements: Muscle, sperm tail, flagellagenerally located where energy consumption is highest in the cellMitochondria (fibroblasts)Mitochondria (sperm)

Packed around initial segmentEnergy for sperm motility, microtubules (9+2)

Maternal InheritanceMost animals

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. PMID 24528894mouse - suggest a more passive process, prefertilization sperm mtDNA elimination and uneven mitochondrial distribution in embryos. PMID 23878233(image (http://www.pnas.org/content/110/32/13038/F2.expansion.html))

Recent experiments using swapping maternal mitochondrial DNA in mammalian oocytes (image (http://embryology.med.unsw.edu.au/embryology/index.php?

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(/cellbiology/index.php/File:Mitochondrial_membraneous_compartments.jpg)Mitochondrial membraneous compartments

(/cellbiology/index.php/File:Eukaryotic_mitochondrial_genomes.jpg)Eukaryotic mitochondrial genomes

title=File:Swapping_mitochondrial_DNA_mammalian_oocytes.jpg))

Mitochondria ComponentsOuter Membrane

porin - membrane channel, allows ions and metabolites into the mitochondria (<5000 daltons)

Intermembrane Spacesimilar to the cytosol with respect to the small molecules it containsalso enzymes that use ATP

Inner Membrane

(/cellbiology/index.php/File:Cardiolipin.jpg)

cardiolipin - phospholipid, makes membrane impermeable to ions (unique to mitochondria inner membrane)mitochondrial damage and depolarization causes cardiolipin translocation to the outer mitochondrialmembrane to initiate mitophagy (selective degradation of mitochondria by autophagy)

transport proteins - permeable to molecules required in the matrix

Cristaeincrease inner membrane surface area

tubular, vesicular or flat cristaeAdenosine triphosphate (ATP) synthaserespiratory electron transfer chain proteinstransport proteins

Links: Model - inner boundary membrane and cristae membranes (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078762/figure/F1/)

Matrixmetabolic 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

Mitochondria DNAdouble stranded circular DNA (mitoDNA. mtDNA)1981 complete human sequence (16,569 nucleotides)37 genes

encodes 13 polypeptides involved in oxidative phosphorylationremaining genes transfer RNA (tRNA) and ribosomal RNA (rRNA)

multiple copies within the matrixmaternally inheritedremainder encoded by nuclear DNAproteins made in cytosol and imported into mitochondria

Links: Home Reference - Mitochondrial DNA (http://ghr.nlm.nih.gov/chromosome=MT%7CGenetics)

Mitochondria Protein Synthesisyeast - Petite mutants

all mitochondrion-encoded gene products missingforms small anaerobic coloniesorganelle is constructed entirely from nucleus-encoded proteins

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(/cellbiology/index.php/File:Proteintransport.gif)

Many mitochondrial proteins are encoded by nuclear DNA

synthesis begins in the cell cytoplasmimported into the mitochondria

targeting similar to signal sequence for RERonce in matrix signal sequence is cleaved (by Hsp70)

protein then folds (by Hsp60)proteins for mitochondrial membrane or intermembranous spaceadditional 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 acidsat the N terminus.

Links: Replication and preferential inheritance of hypersuppressive petite mitochondrial DNA (http://www.nature.com/emboj/journal/v20/n7/full/7593682a.html) |Home Reference - Mitochondrial DNA (http://ghr.nlm.nih.gov/chromosome=MT%7CGenetics)

Mitochondrial Division and FusionMitochondria Fission

Mitochondrial DivisionDivide independently of thewhole cell cycleGenerated by existingmitochondriainward furrowing likebacterial division

mitochondria lack FtsZring (seen in bacteria)rely on dynamin on thecytosolic face for fission

(/cellbiology/index.php/File:Mitochondrial_fission.jpg)Mitochondrial fission

(/cellbiology/index.php/File:Mitochondria_fission_and_autophagy.jpg)

Blocking mitochondrial fission causes autophagy

Mitochondrial inheritance

Mitochondrial Fusion

when two separate mitochondria join as onefission and fusion considered to be balanceddisruption causes normal tubular network of mitochondria to fragment intoshort rods or spheresRequires large GTPasesMitofusins 1 and 2 (Mfn1, Mfn2) and OPA1

Mfn1 and Mfn2 for outer membrane fusionOPA1 for inner membrane fusion

(/cellbiology/index.php/File:Mitochondrial_fusion_EM.jpg)Mitochondrial fusion (EM)

Links: Preventing Mitochondrial Fission Impairs Mitochondrial Function and Leads to Loss of Mitochondrial DNA(http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003257) | Mitochondrial dynamics–fusion, fission, movement, and mitophagy–inneurodegenerative diseases (http://hmg.oxfordjournals.org/cgi/content/full/18/R2/R169)]

Energy Production

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(/cellbiology/index.php/File:Mitochondrial_morphology.jpg)Mitochondrial morphologies during apoptosis

Electrochemical proton gradient across the inner mitochondrial membrane is used to drive ATP synthesis MBoC - The general mechanism of oxidativephosphorylation (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A2489&rendertype=figure&id=A2514)

Respiration

Raw MaterialsOxygenPyruvate & Fatty Acids

ProductsCarbon DioxideAdenosine Triphosphate (ATP)

Steroid Synthesisadrenal glands and gonads/ovaries - Steroid hormones required for carbohydrate metabolism, stress management, and reproduction and are synthesized fromcholesterol in mitochondria of these tissues. PMID 25505173

Mitophagyhttp://jcb.rupress.org/content/208/7/865.full (http://jcb.rupress.org/content/208/7/865.full)

ApoptosisMitochondria in addition to energy production, have a second major function related to programmed cell deathby apoptosis.

cytochrome C release activates caspasesother changes include

electron transport, loss of mitochondrial transmembrane potentialaltered cellular oxidation-reductionBcl-2 family proteins (pro- and antiapoptotic)

Vesicular Mitochondriabegin to appear during the release of cytochrome C which initiates mitochondrial mediated apoptosistransformation from normal morphologywith an inner boundary membrane connected to lamellar cristae via crista junctionsmultiple vesicular matrix compartmentsfacilitates membrane fission or fragmentation as the matrix is fragmented at this stagefragmentation of the mitochondrion requires only outer membrane fission

(/cellbiology/index.php/File:Apoptosis_mitochondria.jpg)

Apoptosis mitochondrial pathway (MH- this topic will be covered again in detail in the Cell Death Lecture(/cellbiology/index.php/Cell_Death_2#Mitochondrial_Pathway))

Links: Lecture - Cell Death 1 (/cellbiology/index.php/Cell_Death_1) | Lecture - Cell Death 2 (/cellbiology/index.php/Cell_Death_2) | Movie - Vesicular Mitochondria(http://www.sci.sdsu.edu/TFrey/vesicularmitomovies/Vesicular.htm) | Role of mitochondria in apoptosis(http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/mito.htm) | Ibioseminar - Apoptosis Part 2: Factors Involved in the Intrinsic Pathway of Apoptosis (27:39minutes) (http://www.ibioseminars.org/index.php?option=com_content&view=article&id=181&Itemid=178)

MethodsDynabead Isolation

Mitochondria isolation using magnetic beads conjugated to antibodies to mitochondrial surface markers.

MitoTracker Probes

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(/cellbiology/index.php/File:Mitochondrial_DNA_-_Human_polymorphic_numts.png)Human polymorphic numts PMID 15361937

MitoTracker probes are cell-permeant mitochondrion-selective dyes.

Links: Bovine pulmonary artery endothelial cells (BPAEC) - LysoTracker Red and MitoTracker Green(http://tools.invitrogen.com/content/sfs/gallery/high/g001829.jpg) | Bovine pulmonary artery endothelial cell - probes to mitochondria (red), peroxisomes (green),and the nucleus (blue) (http://tools.invitrogen.com/content/sfs/gallery/high/g002238.jpg) | Molecular Probes - Probes for Mitochondria(http://www.invitrogen.com/site/us/en/home/References/Molecular-Probes-The-Handbook/Probes-for-Organelles/Probes-for-Mitochondria.html) | Spectralcharacteristics of the MitoTracker probes (http://www.invitrogen.com/site/us/en/home/References/Molecular-Probes-The-Handbook/tables/Spectral-characteristics-of-the-MitoTracker-probes.html)

Apoptosis AssaysCytochrome c Releasing Apoptosis Assays - detection of cytochrome c translocation from mitochondria into cytosol during apoptosis. Commercial Kit PDF(http://www.kamiyabiomedical.com/pdf/KT-147.pdf)

Cytochrome c normally located in the space between the inner and outer mitochondrial membranesMitochondrial transmembrane potential changes (JC-1, cationic dye) Commercial Kit 1 (http://www.genscript.com/kit/L00291-Mitochondrial_Apoptosis_Detection_Kit_JC-1.html) | Commercial Kit 2 (http://www.millipore.com/cellbiology/cb3/mitolight)

Healthy cells - accumulates and aggregates in the mitocondria, bright red fluorescence.Apoptotic cells - altered mitochondrial transmembrane potential causes dye to remain in the cytoplasm in monomer form, green fluorescence.

MitoChipMicroarray of both strands of the entire human mitochondrial coding sequence (15,451 bp).

detecting germ line and heteroplasmic mutations by complete mitochondrial genome resequencing Affymetrix Commercial Microarray(http://www.affymetrix.com/browse/products.jsp?productId=131460&navMode=34000&navAction=jump&aId=productsNav) Manual(http://www.affymetrix.com/support/technical/manuals.affx)

oligonucleotide probes synthesized using standard photolithography and solid-phase synthesis, and is able to sequence >29 kb of double-stranded DNA in asingle assay.

The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection. Maitra A, Cohen Y, Gillespie SE, Mambo E, Fukushima N,Hoque MO, Shah N, Goggins M, Califano J, Sidransky D, Chakravarti A. Genome Res. 2004 May;14(5):812-9. PMID: 15123581(http://www.ncbi.nlm.nih.gov/pubmed/15123581) | http://genome.cshlp.org/content/14/5/812.abstract (http://genome.cshlp.org/content/14/5/812.abstract) GenomeRes. 2004]

AbnormalitiesNuclear transfer of mitochondrial DNA

mitochondria to the nucleus generates nuclear copies of mitochondrial DNA (numts)Integration can appear as neutral polymorphism or associated with human diseases (insertion of mtDNA intogenes,5 known cases), the mitochondrial genome remains intact in the individuals.

1. insertion at the breakpoint junction of a reciprocal translocation between chromosome 9 and 11.2. insertion into splice site mutation in the human gene for plasma factor VII (causes severe plasma factor VII

deficiency, bleeding disease)3. insertion into exon 14 of the GLI3 gene causes a premature stop codon (associated with Chernobyl)4. insertion into exon 2 of MCOLN1, eliminated proper splicing of the gene (mucolipidosis IV).5. insertion in exon 9 of the USH1C gene (Usher syndrome type IC)

Above examples from: PMID: 15361937 (http://www.ncbi.nlm.nih.gov/pubmed/15361937)

Mitochondrial MyopathiesA group of several diseases

Kearns-Sayre syndrome (KSS) Genes and Disease - Kearns-Sayre syndrome(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.385)Leigh's syndrome Genes and Disease - Leigh's syndrome (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.387)mitochondrial DNA depletion syndrome (MDS)mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) Genes and Disease - MELAS(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.389)myoclonus epilepsy with ragged red fibers (MERRF)mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)neuropathy, ataxia and retinitis pigmentosa (NARP) Genes and Disease - NARP (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.388)Pearson syndrome Genes and Disease - Pearson syndrome (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.390)Progressive external ophthalmoplegia (PEO) Genes and Disease - Progressive External Ophthalmoplegia (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=gnd.section.391)

Friedreich's ataxia (FRDA)mutation in gene for frataxin (a mitochondrial iron (Fe) chaperone)mechanism may be a mitochondrial iron (Fe) loading and reactive oxygen speciesanimal models show H2O2 is an important pathogenic substrate underlying the phenotypes arising from frataxin deficiencyGenes and Diseases - Friedreich's ataxia (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=gnd.section.205)

Charcot–Marie–Tooth type 2Ainherited neuropathycaused by mutations in mitofusin 2

proper regulation of mitochondrial dynamics required in neurons

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(/cellbiology/index.php/File:Leber_hereditary_optic_neuropathy.jpg)Leber hereditary optic neuropathy

Leber Hereditary Optic Neuropathymaternally inherited cause of blindness Genes and Diseases - LHOM(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.386)mutation of mitochondrial DNA (mtDNA)

three common mtDNA mutations: G11778A, T14484C, G3460A

Aminoglycoside-induced deafnessdue to aminoglycoside antibiotic treatment Genes and Diseases - Aminoglycoside-induced deafness(http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.384)

gentamycin, streptomycin, and tobramcyinsimilarity of mitochondrial ribosomes to bacterial ribosomes

OtherAdenoid Cystic Carcinoma (ACC)Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands. Mithani SK, Shao C, Tan M, SmithIM, Califano JA, El-Naggar AK, Ha PK. PLoS One. 2009 Dec 30;4(12):e8493. PMID: 20041111(http://www.ncbi.nlm.nih.gov/pubmed/20041111)

"Mitochondrial mutation is frequent in salivary ACCs. The high incidence of amino acid changing mutations implicates alterations in aerobic respiration in ACCcarcinogenesis. D-loop mutations are of unclear significance, but may be associated with alterations in transcription or replication."

Cyclic Vomiting Syndrome?Links: Genes and Diseases -Mitochondria and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=gnd.chapter.383) | GeneReviews - Mitochondrial DisordersOverview (http://www.genetests.org/query?dz=mt-overview) | Genes and Diseases - Friedreich's ataxia (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=gnd.section.205) | Muscular Dystrophy Association - Mitochondrial Myopathies (http://www.mda.org/disease/mito.html) | The Cleveland Clinic - MitochondrialMyopathies (http://www.clevelandclinic.org/health/health-info/docs/1600/1678.asp?index=6957) | Genes and Diseases(http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/gnd/tocstatic.html) | OMIM - Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim)

ReferencesTextbooksEssential Cell Biology

Chapter 13 Energy Generation in Mitochondria and ChloroplastsChapter 14 Intracellular Compartments and Transport

Molecular Biology of the CellAlberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

The Mitochondrion (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.2495)

Molecular Cell BiologyLodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.section.1182#1189)Figure 16-7. A three-dimensional diagram of a mitochondrion cut longitudinally (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.figgrp.4346)

The Cell- A Molecular ApproachCooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

The Cell - A Molecular Approach - III. Cell Structure and Function 10. Bioenergetics and Metabolism - Mitochondria, Chloroplasts, and PeroxisomesMitochondria (http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.1625)

Search Online Textbooks"mitochondria" Molecular Biology of the Cell (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=mitochondria+mboc4) | Molecular CellBiology (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=mitochondria+mcb) | The Cell- A molecular Approach(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=mitochondria+cooper) | Bookshelf (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=mitochondria)"chloroplast" Molecular Biology of the Cell (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=chloroplast+mboc4) | Molecular CellBiology (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=chloroplast+mcb) | The Cell- A molecular Approach(http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=chloroplast+cooper) | Bookshelf (http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=chloroplast)

Books

PubMedPubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedicalarticles back to 1948. PubMed includes links to full text articles and other related resources. PubMed (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed)PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the NationalLibrary of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC (http://www.ncbi.nlm.nih.gov/sites/entrez?db=PMC)Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews inOMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM (http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim)Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences,Protein Structures, Complete Genomes, Taxonomy, and others Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar)

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Search Pubmed"mitochondria" PubMed reviews (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=mitochondria+review) | PubMed all articles(http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=mitochondria) | PMC reviews (http://www.ncbi.nlm.nih.gov/sites/entrez?db=PMC&cmd=search&term=mitochondria+review) | PMC all articles (http://www.ncbi.nlm.nih.gov/sites/entrez?db=PMC&cmd=search&term=mitochondria) |OMIM (http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim&cmd=search&term=mitochondria) | Entrez all databases (http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=mitochondria)

ReviewsMichael R Duchen, Gyorgy Szabadkai Roles of mitochondria in human disease. Essays Biochem.: 2010, 47;115-37 PubMed 20533904(http://www.ncbi.nlm.nih.gov/pubmed/20533904)

Andrew B Knott, Guy Perkins, Robert Schwarzenbacher, Ella Bossy-Wetzel Mitochondrial fragmentation in neurodegeneration. Nat. Rev. Neurosci.: 2008,9(7);505-18 PubMed 18568013 (http://www.ncbi.nlm.nih.gov/pubmed/18568013)

David C Chan Mitochondria: dynamic organelles in disease, aging, and development. Cell: 2006, 125(7);1241-52 PubMed 16814712(http://www.ncbi.nlm.nih.gov/pubmed/16814712)

Hsiuchen Chen, David C Chan Emerging functions of mammalian mitochondrial fusion and fission. Hum. Mol. Genet.: 2005, 14 Spec No. 2;R283-9 PubMed16244327 (http://www.ncbi.nlm.nih.gov/pubmed/16244327)

ArticlesBcl-x L increases mitochondrial fission, fusion, and biomass in neurons. Berman SB, Chen YB, Qi B, McCaffery JM, Rucker EB 3rd, Goebbels S, Nave KA,Arnold BA, Jonas EA, Pineda FJ, Hardwick JM. J Cell Biol. 2009 Mar 9;184(5):707-19. Epub 2009 Mar 2. PMID: 19255249(http://www.ncbi.nlm.nih.gov/pubmed/19255249)

Mitochondrion ImagesFor a full selection of see Cell Biology Images - Mitochondria Images (/cellbiology/index.php/Mitochondria_Images)

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cell from lung (tem)

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cell from lung (tem)

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Mitochondria (tem)

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cell from lung (tem)

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Cardiac musclemitochondria (tem)

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Heart mitochondria (tem)

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Heart_papillary_muscle(tem)

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Morphological changesin the cellularmitochondrial networkduring mitosis

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Mitochondrion structurecartoon

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Mitochondrialmembraneouscompartments

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Mitochondrion rat liver

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Eukaryotic mitochondrialgenomes

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Mitochondrial ROSproduction

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Mitochondrial genomeand the oxidativephosphorylation pathway

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Apoptosis pathwaycartoon

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Models of MitochondrialMembranePermeabilization

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Viral ProteinsMitochondrial MembranePermeabilization

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Negative_Bax.jpg)

Bcl-XL Functions Like aDominant-Negative Bax

Mitotracker (http://www.lifetechnologies.com/order/catalog/product/M7512)

MoviesMitochondrial replication factories DNA replication factories (http://jcb.rupress.org/cgi/content/full/jcb.200304040/DC1/4) in mitochondria divide(http://jcb.rupress.org/cgi/content/full/jcb.200304040/DC1/3) even in the absence of mitochondrial DNA, according to Meeusen and Nunnari(http://jcb.rupress.org/cgi/content/abstract/163/3/503).Apoptotic cells show a transient loss in mitochondrial membrane potential Waterhouse et al. (http://jcb.rupress.org/cgi/content/abstract/153/2/319)suggest that the transient (http://jcb.rupress.org/cgi/content/full/153/2/319/F4/DC1) loss of mitochondrial membrane potential that can be seen in individual

Page 10: Cell Mitochondria - CellBiology · PDF fileCell Mitochondria Introduction ... Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase Evolution Mitochondria

(http://moodle.telt.unsw.edu.au/course/view.php?id=25143)Moodle

apoptotic cells may be masked by cell-to-cell asynchrony when looking at a population of cells.Mitochondria slow down for calcium Mitochondria move along microtubules (http://jcb.rupress.org/cgi/content/full/jcb.200406038/DC1/2), but Yi et al.(http://jcb.rupress.org/cgi/content/abstract/167/4/661) find that they slow down (http://jcb.rupress.org/cgi/content/full/jcb.200406038/DC1/1) when calciumlevels rise, probably so that they can help buffer the ion back to normal levels.

2017 Course ContentLectures: Cell Biology Introduction (/cellbiology/index.php/Cell_Biology_Introduction) | Cells Eukaryotes and Prokaryotes(/cellbiology/index.php/Cells_Eukaryotes_and_Prokaryotes) | Cell Membranes and Compartments(/cellbiology/index.php/Cell_Membranes_and_Compartments) | Cell Nucleus (/cellbiology/index.php/Cell_Nucleus) | Cell Export - Exocytosis(/cellbiology/index.php/Cell_Export_-_Exocytosis) | Cell Import - Endocytosis (/cellbiology/index.php/Cell_Import_-_Endocytosis) | CytoskeletonIntroduction (/cellbiology/index.php/Cytoskeleton_Introduction) | Cytoskeleton - Microfilaments (/cellbiology/index.php/Cytoskeleton_-_Microfilaments) | Cytoskeleton - Microtubules (/cellbiology/index.php/Cytoskeleton_-_Microtubules) | Cytoskeleton - Intermediate Filaments(/cellbiology/index.php/Cytoskeleton_-_Intermediate_Filaments) | Cell Mitochondria | Cell Junctions (/cellbiology/index.php/Cell_Junctions) |Extracellular Matrix 1 (/cellbiology/index.php/Extracellular_Matrix_1) | Extracellular Matrix 2 (/cellbiology/index.php/Extracellular_Matrix_2) | CellCycle (/cellbiology/index.php/Cell_Cycle) | Cell Division (/cellbiology/index.php/Cell_Division) | Cell Death 1 (/cellbiology/index.php/Cell_Death_1)| Cell Death 2 (/cellbiology/index.php/Cell_Death_2) | Signal 1 (/cellbiology/index.php/Signal_1) | Signal 2 (/cellbiology/index.php/Signal_2) | Stem Cells 1(/cellbiology/index.php/Stem_Cells_1) | Stem Cells 2 (/cellbiology/index.php/Stem_Cells_2) | Development (/cellbiology/index.php/Development) | 2017 Revision(/cellbiology/index.php/2017_Revision)

2017 Laboratories: Introduction to Lab (/cellbiology/index.php/2017_Lab_1) | Fixation and Staining (/cellbiology/index.php/2017_Lab_2) |

2017 Projects (/cellbiology/index.php/ANAT3231_Projects_2017): Group 1 - Delta (/cellbiology/index.php/2017_Group_1_Project) | Group 2 - Duct(/cellbiology/index.php/2017_Group_2_Project) | Group 3 - Beta (/cellbiology/index.php/2017_Group_3_Project) | Group 4 - Alpha(/cellbiology/index.php/2017_Group_4_Project)

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G

Categories (/cellbiology/index.php/Special:Categories): Science-Undergraduate (/cellbiology/index.php/Category:Science-Undergraduate)2017ANAT3231 (/cellbiology/index.php/Category:2017ANAT3231) Organelle (/cellbiology/index.php?title=Category:Organelle&action=edit&redlink=1)Mitochondria (/cellbiology/index.php/Category:Mitochondria)

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