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CellularRespiration
Cellularrespirationistheprocessofoxidizingfoodmolecules,like
glucose,tocarbondioxideandwater.
C6H12O6+6O2+6H2O12H2O+6CO2
TheenergyreleasedistrappedintheformofATPforusebyallthe
energyconsumingactivitiesofthecell.

Indextothispage
Mitochondria
TheCitricAcidCycle
TheElectronTransportChain
ChemiosmosisinMitochondria
HowmanyATPs?
MitochondrialDNA(mtDNA)

Theprocessoccursintwophases:
glycolysis,thebreakdownofglucosetopyruvicacid
thecompleteoxidationofpyruvicacidtocarbondioxideandwater
Ineukaryotes,glycolysisoccursinthecytosol.(Linktoadiscussionofglycolysis).Theremainingprocesses
takeplaceinmitochondria.

Mitochondria
Mitochondriaaremembraneenclosedorganellesdistributedthroughthecytosolofmosteukaryoticcells.
Theirnumberwithinthecellrangesfromafewhundredto,inveryactivecells,thousands.Theirmain
functionistheconversionofthepotentialenergyoffoodmoleculesintoATP.
Mitochondriahave:
anoutermembranethatenclosestheentirestructure
aninnermembranethatenclosesafluidfilledmatrix
betweenthetwoistheintermembranespace
theinnermembraneiselaboratelyfoldedwithshelflikecristae
projectingintothematrix.
asmallnumber(some510)circularmoleculesofDNA
Thiselectronmicrograph(courtesyofKeithR.Porter)
showsasinglemitochondrionfromabatpancreascell.
Notethedoublemembraneandthewaytheinner
membraneisfoldedintocristae.Thedark,membrane
boundedobjectsabovethemitochondrionare
lysosomes.

Thenumberofmitochondriainacellcan
increasebytheirfission(e.g.followingmitosis)
decreasebytheirfusingtogether.
(Defectsineitherprocesscanproduceserious,evenfatal,illness.)

TheOuterMembrane
Theoutermembranecontainsmanycomplexesofintegralmembraneproteinsthatformchannelsthrough
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whichavarietyofmoleculesandionsmoveinandoutofthemitochondrion.

TheInnerMembrane
Theinnermembranecontains5complexesofintegralmembraneproteins:
NADHdehydrogenase(ComplexI)
succinatedehydrogenase(ComplexII)
cytochromecreductase(ComplexIIIalsoknownasthecytochromebc1complex)
cytochromecoxidase(ComplexIV)
ATPsynthase(ComplexV)

TheMatrix
Thematrixcontainsacomplexmixtureofsolubleenzymesthatcatalyzetherespirationofpyruvicacidand
othersmallorganicmolecules.
Herepyruvicacidis
oxidizedbyNAD+ producingNADH
+H+
decarboxylatedproducingamolecule
of
carbondioxide(CO2)and
a2carbonfragmentofacetate
boundtocoenzymeAforming
acetylCoA

TheCitricAcidCycle
This2carbonfragmentisdonatedtoa
moleculeofoxaloaceticacid.
Theresultingmoleculeofcitricacid
(whichgivesitsnametotheprocess)
undergoestheseriesofenzymaticsteps
showninthediagram.
Thefinalstepregeneratesamolecule
ofoxaloaceticacidandthecycleis
readytoturnagain.
Summary:
Eachofthe3carbonatomspresentinthepyruvatethatenteredthemitochondrionleavesasamolecule
ofcarbondioxide(CO2).
At4steps,apairofelectrons(2e)isremovedandtransferredtoNAD+reducingittoNADH+H+.
Atonestep,apairofelectronsisremovedfromsuccinicacidandreducestheprostheticgroupflavin
adeninedinucleotide(FAD)toFADH2.
TheelectronsofNADHandFADH2aretransferredtotheelectrontransportchain.

TheElectronTransportChain
Theelectrontransportchainconsistsof3complexesofintegralmembraneproteins
theNADHdehydrogenasecomplex(I)
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thecytochromecreductasecomplex(III)
thecytochromecoxidasecomplex(IV)
andtwofreelydiffusiblemolecules
ubiquinone
cytochromec
thatshuttleelectronsfromonecomplextothenext.
Theelectrontransportchainaccomplishes:
thestepwisetransferofelectronsfromNADH(andFADH2)to
oxygenmoleculestoform(withtheaidofprotons)water
molecules(H2O)
(Cytochromeccanonlytransferoneelectronatatime,so
cytochromecoxidasemustwaituntilithasaccumulated4ofthem
beforeitcanreactwithoxygen.)
harnessingtheenergyreleasedbythistransfertothepumpingof
protons(H+)fromthematrixtotheintermembranespace.
Approximately20protonsarepumpedintotheintermembrane
spaceasthe4electronsneededtoreduceoxygentowaterpassthroughtherespiratorychain.
Thegradientofprotonsformedacrosstheinnermembranebythisprocessofactivetransportformsa
miniaturebattery.
TheprotonscanflowbackdownthisgradientonlybyreenteringthematrixthroughATPsynthase,
anothercomplex(complexV)of16integralmembraneproteinsintheinnermembrane.Theprocessis
calledchemiosmosis.

Chemiosmosisinmitochondria
TheenergyreleasedaselectronspassdownthegradientfromNADHtooxygenisharnessedbythree
enzymecomplexesoftherespiratorychain(I,III,andIV)topumpprotons(H+)againsttheirconcentration
gradientfromthematrixofthemitochondrionintotheintermembranespace(anexampleofactive
transport).

Astheirconcentrationincreasesthere(whichisthesameassayingthatthepHdecreases),astrongdiffusion
gradientissetup.TheonlyexitfortheseprotonsisthroughtheATPsynthasecomplex.Asinchloroplasts,
theenergyreleasedastheseprotonsflowdowntheirgradientisharnessedtothesynthesisofATP.The
processiscalledchemiosmosisandisanexampleoffacilitateddiffusion.
Onehalfofthe1997NobelPrizeinChemistrywasawardedtoPaulD.BoyerandJohnE.Walkerfortheir
discoveryofhowATPsynthaseworks.Linktosomeofthedetails.
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ExternalLink
ScrolldownthelefthandcolumnatthislinktoviewanimationsofATPsynthase,the
electrontransportchainandotherson"cellularenergyconversion".
Pleaseletmeknowbyemailifyoufindabrokenlinkinmypages.)

HowmanyATPs?
ItistemptingtotrytoviewthesynthesisofATPasasimplematterofstoichiometry(thefixedratiosof
reactantstoproductsinachemicalreaction).But(with3exceptions)itisnot.
MostoftheATPisgeneratedbytheprotongradientthatdevelopsacrosstheinnermitochondrialmembrane.
ThenumberofprotonspumpedoutaselectronsdropfromNADHthroughtherespiratorychaintooxygenis
theoreticallylargeenoughtogenerate,astheyreturnthroughATPsynthase,3ATPsperelectronpair(but
only2ATPsforeachpairdonatedbyFADH2).
With12pairsofelectronsremovedfromeachglucosemolecule,
10byNAD+ (so10x3=30)and
2byFADH2(so2x2=4),
thiscouldgenerate34ATPs.
Addtothisthe4ATPsthataregeneratedbythe3exceptionsandonearrivesat38.
But
Theenergystoredintheprotongradientisalsousedfortheactivetransportofseveralmoleculesand
ionsthroughtheinnermitochondrialmembraneintothematrix.
NADHisalsousedasreducingagentformanycellularreactions.
SotheactualyieldofATPasmitochondriarespirevarieswithconditions.Itprobablyseldomexceeds30.

Thethreeexceptions
AstoichiometricproductionofATPdoesoccurat:
onestepinthecitricacidcycleyielding2ATPsforeachglucosemolecule.Thisstepistheconversion
ofalphaketoglutaricacidtosuccinicacid.
attwostepsinglycolysisyielding2ATPsforeachglucosemolecule.

MitochondrialDNA(mtDNA)
Thehumanmitochondrioncontains510identical,circularmoleculesofDNA.Eachconsistsof16,569base
pairscarryingtheinformationfor37geneswhichencode:
2differentmoleculesofribosomalRNA(rRNA)
22differentmoleculesoftransferRNA(tRNA)(atleastoneforeachaminoacid)
13polypeptides
TherRNAandtRNAmoleculesareusedinthemachinerythatsynthesizesthe13polypeptides.
The13polypeptidesparticipateinbuildingseveralproteincomplexesembeddedintheinnermitochondrial
membrane.
7subunitsthatmakeupthemitochondrialNADHdehydrogenase(complexI)
cytochromeb,asubunitofcytochromecreductase(complexIII)
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3subunitsofcytochromecoxidase(complexIV)
2subunitsofATPsynthase(complexV)
Eachoftheseproteincomplexesalsorequiressubunitsthatare
encodedbynucleargenes,synthesizedinthecytosol,and
importedfromthecytosolintothemitochondrion.Nucleargenes
alsoencode~1,000otherproteinsthatmustbeimportedintothe
mitochondrion.[More]

MutationsinmtDNAcausehumandiseases.
Mutationsin12ofthe13polypeptideencodingmitochondrial
geneshavebeenfoundtocausehumandisease.
Althoughmanydifferentorgansmaybeaffected,disordersofthe
musclesandbrainarethemostcommon.Perhapsthisreflectsthe
greatdemandforenergyofboththeseorgans.(Although
representingonly~2%ofourbodyweight,thebrainconsumes~20%oftheenergyproducedwhenweareat
rest.)
Someofthesedisordersareinheritedinthegermline.Ineverycase,themutantgeneisreceivedfromthe
motherbecausenoneofthemitochondriainspermsurvivesinthefertilizedegg.Otherdisordersaresomatic
thatis,themutationoccursinthesomatictissuesoftheindividual.
Example:exerciseintolerance
Anumberofhumanswhosufferfromeasilyfatiguedmusclesturnouttohaveamutationsintheir
cytochromebgene.Curiously,onlythemitochondriaintheirmuscleshavethemutationthemtDNAof
theirothertissuesisnormal.Presumably,veryearlyintheirembryonicdevelopment,amutationoccurredin
acytochromebgeneinthemitochondrionofacelldestinedtoproducetheirmuscles.
Theseverityofmitochondrialdiseasesvariesgreatly.Thereasonforthisisprobablytheextensivemixingof
mutantDNAandnormalDNAinthemitochondriaastheyfusewithoneanother.Amixtureofbothiscalled
heteroplasmy.Thehighertheratioofmutanttonormal,thegreatertheseverityofthedisease.Infactby
chancealone,cellscanonoccasionendupwithalltheirmitochondriacarryingallmutantgenomesa
conditioncalledhomoplasmy(aphenomenonresemblinggeneticdrift).
MitochondrialReplacementTechniques
AsInotedabove,onlymotherscanpassmutantmtDNAontotheiroffspring.Twotechniquesareunder
intenseinvestigation,eitherofwhichcouldenableamothertohavechildrenfreeofdefectivemitochondria.
Thesetechniques(numbers1and2)aredescribedonanotherpage[Linktoit].
Mutationsinsome228nucleargeneshavealsobeenimplicatedinhumanmitochondrialdiseases,but
mitochondrialreplacementtechniqueswillnotbeabletohelpwiththese.

Whydomitochondriahavetheirowngenome?
Manyofthefeaturesofthemitochondrialgeneticsystemresemblethosefoundinbacteria.Thishas
strengthenedthetheorythatmitochondriaaretheevolutionarydescendantsofabacteriumthatestablishedan
endosymbioticrelationshipwiththeancestorsofeukaryoticcellsearlyinthehistoryoflifeonearth.
However,manyofthegenesneededformitochondrialfunctionhavesincemovedtothenucleargenome.
TherecentsequencingofthecompletegenomeofRickettsiaprowazekiihasrevealedanumberofgenes
closelyrelatedtothosefoundinmitochondria.Perhapsrickettsiasaretheclosestlivingdescendantsofthe
endosymbiontsthatbecamethemitochondriaofeukaryotes.
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FurtherdiscussionoftheevolutionaryimplicationsofmtDNA.
Welcome&NextSearch
27March2016

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