rion itself. In comparison to the DNA in the nucleus of the cell (nDNA), mtDNA is easily damaged by free radicals and the ROS that it produces. Freely floating mtDNA lacks protective measures associated with nDNA, and therefore suffers from multiple mutations. It has been estimated that the lack of protective measures results in mutations to mtDNA occurring 10 to 20 times more frequently than mutations to nDNA.
Mitochondrial damage and/or dysfunction contribute to various disease states. Some diseases are due to mutations or deletions in the mitochondrial genome. Mitochondria divide and proliferate with a faster turnover rate than their host cells, and their replication is under control of the nuclear genome. If a threshold proportion of mitochondria in a cell is defective, and if a threshold proportion of such cells within a tissue have defective mitochondria, symptoms of tissue or organ dysfunction can result. Practically any tissue can be affected, and a large variety of symptoms can be present, depending on the extent to which different tissues are involved.
A fertilized ovum might contain both normal and genetically defective mitochondria. The segregation of defective mitochondria into different tissues during division of this ovum is a stochastic process, as will be the ratio of defective to normal mitochondria within a given tissue or cell (although there can be positive or negative selection for defective mitochondrial genomes during mitochondrial turnover within cells). Thus, a variety of different pathologic phenotypes can emerge out of a particular point mutation in mitochondrial DNA. Conversely, similar phenotypes can emerge from mutations or deletions affecting different genes within mitochondrial DNA. Clinical symptoms in congenital mitochondrial diseases often manifest in postmitotic tissues with high energy demands like brain, muscle, optic nerve, and myocardium, but other tissues including endocrine glands, liver, gastrointestinal tract, kidney, and hematopoietic tissue are also involved, again depending in part on the segregation of mitochondria during development, and on the dynamics of mitochondrial turnover over time.
In addition to congenital disorders involving inherited defective mitochondria, acquired mitochondrial damage and/or dysfunction contribute to diseases, particularly neurodegenerative disorders associated with aging like Parkinson's, Alzheimer's, Huntington's Diseases. The incidence of somatic mutations in mitochondrial DNA rises exponentially with age; and diminished respiratory chain activity is found universally in aging people. Mitochondrial dysfunction is also implicated in excitotoxic neuronal injury, such as that associated with seizures or ischemia.
Other pathologies with etiology involving mitochondrial damage and/or dysfunction include schizophrenia, bipolar disorder, dementia, epilepsy, stroke, cardiovascular disease, retinal degenerative disease (e.g., age-related macular degeneration, Stargardt's disease
rion itself. In comparison to the DNA in the nucleus of the cell (nDNA), mtDNA is easily damage by spare radicals and the ROS that it produces. Freely floating mtDNA miss protective measures associated with nDNA, and therefore suffer from multiple mutations. It has been estimated that the lack of protective measure results in mutations to mtDNA occur 10 to 20 times more frequently than mutations to nDNA. 
 Mitochondrial price and/or dysfunction contribute to various disease states. Some diseases are due to mutations or omission in the mitochondrial genome. Mitochondria divide and proliferate with a faster turnover pace than their host cells, and their reproduction is under control of the nuclear genome. If a doorway proportion of mitochondria in a cell is defective, and if a threshold proportion of such cell within a tissue have defective mitochondria, symptoms of tissue or organ dysfunction can result. Practically any tissue can be affected, and a large variety of symptoms can be present, depending on the extent to which different tissues are involved. 
 A fertilized ovum might contain both normal and genetically defective mitochondria. The segregation of bad mitochondrion into different tissues during division of this ovum is a stochastic procedure, as will be the ratio of defective to normal mitochondria within a give tissue or cell (although there can be positive or negative selection for bad mitochondrial genomes during mitochondrial turnover within cells). Thus, a variety of different pathologic phenotypes can emerge out of a particular point mutation in mitochondrial DNA. Conversely, exchangeable phenotypes can issue from mutations or deletions affecting different genes within mitochondrial deoxyribonucleic acid. Clinical symptoms in congenital mitochondrial diseases often manifest in postmitotic tissues with high energy demands like brain, brawn, optic boldness, and myocardium, but other tissues include endocrine gland, liver, gastrointestinal tract, kidney, and hematopoietic tissue are also involved, again depending in character on the segregation of mitochondria during development, and on the dynamics of mitochondrial upset over prison term. 
 In addition to congenital disorders involving inherited defective mitochondria, acquired mitochondrial damage and/or dysfunction contribute to diseases, peculiarly neurodegenerative disorders associated with age like Parkinson's, Alzheimer's, Huntington's Diseases. The incidence of somatic mutations in mitochondrial DNA rises exponentially with age; and diminished respiratory chain activeness is found universally in aging people. Mitochondrial dysfunction is also implicated in excitotoxic neuronal wound, such as that associated with seizures or ischemia. 
 early pathology with etiology involving mitochondrial damage and/or dysfunction include schizophrenia, bipolar disorder, dementia, epilepsy, stroke, cardiovascular disease, retinal degenerative disease (for example, age - related macular degeneration, Stargardt's disease
rioj itself. In comparison tu the DNA in thg bucleuv of tge cell (vDNA), mtDNA is easily damaged bt fret radicals and the FOS that pt producws. Fceely floating mvSNA lacks profcctivz neasures assoclated with tDNA, and therexofe suffers from multiple mutations. It has bern estimated thaj the jack of protective measures results in mutatimns to mtDNA pccurring 10 to 20 times more vreqkently than mutatilns to nDNA.
Nitosyondrial damxge and/or dysfunction dontribute to various disease sgates. Some diseqsws wte due to muvationf or deletiokx in tve mitovhondrial genoke. Kitichondria divide and 'roliferate with a fwster turtorer rate than their hisr celns, atd tfwir rekliratjon is unver control of the nucoear genome. If a thtefyold proportikn of iieochondria in a cell is defective, and ix a threshold proportion od such cells within a tissue hwve defective mitochondria, symptoms of tissue or mrgan aysymkctiub fan result. Practically any tissue can be affesfec, snd a large vaviety of symptoms vaj ng present, depevding on fhe extent to whicj diffetent tussues art invplved.
A fertilized ovum mighr contain bonh nirmal and geneticaply defectire mitpchoncria. The segregation of defsctive mitofhondria jvto different tirsuvs dgring division of this ovui is a stichaxtic prucesx, as wyll be the ratio of defective to nlrmal mhtochondriw within a given tissue or cell (although therg cdn te positnve or negative selqction for defgctive micochonarial genojes durmng mitochonqrial turnoves within cellv). Thus, a varuety of difwdrent pathologoc phenotjpts can emeege out of a partigular loint mutation nu nitochondrial DMA. Zondegseky, vimilar phenmtypds zsn emdrge from mmtagionx or deletions affecding different genes wotmin mitocyondrial DNA. Clinical symptoms in congejital mivochoncriwl diseases often manifest in lostmitotlc bissues with righ energy demauds like brain, muscle, optic nerve, and myicardium, but othet tissues including eudpcrine glanvs, livqr, gastrohntestinal tract, kidbey, and hematopoittic tissue are also inbolved, agaij depending in part on the segregation of mitochondria during development, and oi ehe dynamica of mitobhoudrnal turgovec uver time.
In addinion to congenital disorders invulving ithzrited defective mitochondria, azquired mitocfondrial damage and/or dyafunctiom contribute to diseases, particilarly neurodegenerative disordees asaociatvs xith aging like Parkonson's, Alzhwimer's, Yuntlngton's Diseasds. Yhc incidencf of skmatic mutations in mitochondriao DNA eides exponentiallb with age; akd dimihished respiratory chajn adhiviti is found unifersally in agong people. Mitochondgiaj dysfunction ua also implivated it excitotoxir neuronal itjury, such as that associated with seizures or ischgmia.
Other pzthologics with etiology oivolving mitochondrial dsmwge and/of dysfunctiot include schizophrenia, bipolar disorder, dementia, dpijepsy, stroke, cardimvascular disease, vztinal degenerxtive disease (e.g., age-related maculat qegenzration, Stargardt's dpseass
rion itself. In comparison to the DNA nucleus the cell mtDNA is easily the that it produces. floating mtDNA lacks measures associated with nDNA, and therefore from multiple mutations. It has been estimated that the lack of protective measures in mutations to mtDNA occurring 10 to 20 times more frequently than mutations nDNA. damage dysfunction to various disease states. Some diseases are due to mutations or deletions in the mitochondrial genome. divide and proliferate with a faster turnover rate their host cells, and replication is under control of nuclear If a proportion mitochondria a cell is and if a threshold proportion of such cells within a tissue have defective mitochondria, symptoms of tissue organ dysfunction Practically any can affected, a large variety can be present, depending on the different tissues are involved. A fertilized ovum might both normal genetically defective mitochondria. The segregation of mitochondria into different tissues during division of this is a stochastic process, as will be the ratio of defective to normal mitochondria within tissue or cell (although can be positive negative for mitochondrial during mitochondrial within cells). Thus, a variety of different pathologic phenotypes can emerge of a particular point mutation in mitochondrial DNA. Conversely, similar emerge mutations or deletions different genes within mitochondrial Clinical in congenital mitochondrial diseases in tissues demands brain, optic nerve, and myocardium, other tissues including endocrine glands, gastrointestinal tract, kidney, and again depending in part on the segregation of during development, and on the dynamics of turnover over time. In addition to congenital disorders involving inherited defective mitochondria, mitochondrial damage contribute to diseases, particularly neurodegenerative disorders associated with like Parkinson's, Alzheimer's, Huntington's The incidence of somatic mutations in mitochondrial DNA rises with and diminished chain activity is universally in aging Mitochondrial dysfunction is in excitotoxic injury, as seizures or ischemia. Other pathologies with involving damage and/or dysfunction include schizophrenia, disorder, stroke, cardiovascular disease, retinal degenerative disease (e.g., age-related macular degeneration, Stargardt's disease
rion itself. In comparison to tHe DNA in the NucleUs oF thE cEll (ndNA), mTDNA is easily daMAged By free radicals and the ROs that It PRoduCEs. freelY floatiNG mTdnA lAcKs ProTeCTiVe meaSurEs assocIated with ndNA, AnD therefore suFFeRs from multIplE mutations. It Has Been esTiMatED that The Lack oF proteCTive meAsures resUlTS in mutATions to MTdNa occUrring 10 to 20 times more FReQUently than mutaTions tO ndnA.
mITocHonDrial damagE aNd/or dYSfunctiON cONTRibUTe to various diSease states. sOme DiseasEs Are DUe to muTatioNs OR deLetions in thE mitOchondriaL genomE. mitochoNDria divIde and ProLifEratE WiTh A faStER tuRNoVer RAte Than theiR hOsT cellS, and THEIR repLicAtioN is unDer control of tHe nUcleAR geNome. IF a thrEshoLd PropoRtion oF mitoChOndria in a cell is DefeCtive, and iF a tHrEshOlD propORtion oF suCh cElls witHin a tisSUe hAvE DEFeCtive mitochondria, sYmPTOmS of tissuE or orgAN dYsFUnction cAn ResUlt. PRACticaLly aNY tIssue can Be affeCTeD, aNd a largE vAriety Of SymPtoMs can BE preSent, dePending oN the eXTent to which difFErent tissues aRE iNVOlVEd.
A fErtIlized ovum mIght COntaIn boTH nOrmAL and gEnetiCaLLy DEfective mitochondriA. THe segrEgatiOn of defective MitochondrIA INto diffeRent TIsSUes during divisIon of This ovum is A StochastIc proCess, as wiLl be the raTIO of defecTivE to NorMal MIToChondria withiN A GiveN tIssue or CelL (althouGh tHerE caN be PoSitive or nEgative sElEcTiOn For DefecTIve mitocHoNdrIaL geNomes DUring mItochOndrIaL tURnoVer withIN cELLs). ThUs, A vArieTy oF dIfferEnt pAThoLogic phEnotypes cAn eMErge OuT oF a partiCular point mutAtIon in mitocHoNdrIal DNA. cONversely, Similar phenotypes can emeRGe from mUtaTions Or deLetions afFecTing diFfeREnt genEs withIn mitOcHonDRIal DNa. cLiNicAl Symptoms in CONgeNital MiTochOndrial Diseases often manifESt iN postmitotic tIssUes wITH hIgh ENeRGy dEmANds LIKe brain, muscle, opTic nerve, anD mYOcArdium, but oTHer TiSsues inCluding EndocRIne glanDs, liver, gaStrointesTiNal tRACt, kIdney, and heMatopoieTic tissue ARe alsO InVolveD, agAin depEnDinG in paRt on thE SegRegatIon of mItOchondRia duRiNg develoPment, and on the dynamics of MitochOndriAl tUrnover ovEr tIMe.
IN addition To coNgenital diSorDerS invoLviNG inheRiteD DeFecTIve miTochONdria, acquIReD miTOChOndrial damaGE ANd/oR dysfUncTIon conTribUte to diseases, partICularly neurodeGeneRATivE diSOrdeRs Associated with AgiNg LIKe ParkinSoN's, Alzheimer'S, HuntingToN'S DiseAses. ThE incidEnce of sOMAtIC mutatIons In mItochondrIal dNa Rises exPoNeNTially With AgE; and diMinishED resPIRatory chain activIty is FOUnd unIVerSally In Aging peOPle. MItochondriAl dysfunctiOn is alSo imPlicaTed in exCiTotoxiC neUrOnal injury, SUch as that AssocIated wiTh SeizUreS or iscHemiA.
oTher pAthoLoGieS with etioLOGy INvOlVIng MitoChondRiAl daMage and/or DYsfunctiOn iNClude scHiZopHREnia, biPOlAR Disorder, deMenTia, epILEpsy, stroke, CArdiOVaSCular DiseasE, retinAl degenERatIvE diseasE (e.g., AGE-related mAcular degENerAtIon, STargardt'S dIseaSe
rion itself. In comparison  to the DN A inthe  nu cl eusof t he cell (nDNA) ,  mtD NA is easily damaged b y fre er adic a ls  andthe ROS th a t  it  p ro duc es .  F reely  fl oatingmtDNA lack s p ro tective meas u re s associat edwith nDNA, a ndtheref or e s u ffers  fr om mu ltiple mutati ons. It h as been e s timated t ha t th e lack of protect i ve measures resul ts inmu t at i o nstomtDNA occu rr ing 1 0  to 20t im e s mor e  frequently t han mutatio n s t o nDNA .Mit o chondr ial d am a geand/or dysf unct ion contr ibutet o vario u s disea se sta tes . S omed is ea ses  a r e d u etom uta tions or  d el etion s in t h e  mit och ondr ial g enome. Mitoch ond riad ivi de an d pro life ra te wi th a f aster  t urnover rate th an t heir host  ce ll s,an d the i r repl ica tio n is un der con t rol  o f t he  nuclear genome. I fa th resholdpropor t io no f mitoch on dri a in a  cell  isd ef ective,and if ath reshold  p roport io n o f s uch c e llswithin  a tissu e hav e  defective mit o chondria, sym p to m s  o f  tis sue  or organ d ysfu n ctio n ca n  r esu l t. Pr actic al l ya ny tissue can be af fe cted,and a  large variet y of sympt o m s  can bepres e nt ,  depending onthe e xtent to w h ich diff erent  tissues  are invo l v ed.
A fe rti liz edovu m mi ght contain b o t h no rm al andgen eticall y d efe cti vemi tochondri a. The s eg re ga ti onof de f ective m it och on dri a int o  diffe renttiss ue sd uri ng divi s io n of t hi sovum  is  a  stoc hast i c p rocess,  as willbet he r at io  of def ective to nor ma l mitochon dr iawithin a  given t issue or cell (although there c anbe po siti ve or neg ati ve sel ect i on for  defec tivemi toc h o ndria l ge nom es  during mi t o cho ndria lturn over wi thin cells). Thus, a v ariety of dif fer entp a th olo g ic phe no t ype s can emerge outof a parti cu l ar  point mut a tio nin mito chondri al DN A . Conve rsely, si milar phe no type s can  emerge fr om mutat ions or d e letio n saffec tin g diff er ent  gene s with i n m itoch ondria lDNA. C linic al  symptom s in congenital mitocho ndrial  dise ase s often m ani f est  in postm itot ic tissues  wi thhighene r gy de mand s  l ike brain , mu s cle, opti c  n erv e ,  a nd myocardi u m ,  bu t oth ert issues  inc luding endocrineg lands, liver,gast r o int est i naltr act, kidney, a ndhe m a topoieti ctissue arealso inv ol v ed, a gain d ependi ng in p a r to n thesegr ega tion of m ito ch o ndria d ur in g  devel opme nt , andon the dyna m i cs of mitochondr ial t u r nover ove r tim e. 
In add i tion  to congen ital disord ers in volv ing i nherite ddefect ive  m itochondri a , acquire d mit ochondr ia l da mag e and/ or d y s funct ionco ntr ibute tod i se a se s, par ticu larly  n euro degenerat i ve disor der s  associ at edw i th agi n gl i ke Parkins on' s, Al z h eimer's, H u ntin g to n 's Di seases . Theinciden c e o fsomatic  mu t a tions inmitochond r ial  D NA r ises exp on enti al lywi th age; and dim inishedrespirat o r y chai n a c tivi t y is f ou nd universal ly in  a g ing peo p l e.Mitocho n dri aldys func tio n is also implicated in excit otox ic ne u ron al in jury,  s uch as t h at a ssociate d  with seizure s or ischemia.O the r  pat hol o gi es  with eti olo g y inv olvi ngmito cho ndri a l  dam a ge a n d/ or d ysfunc tion  i nc lude schi zo phrenia ,  bip o lar  dis order ,de m en tia, ep ilepsy,strok e,  cardiova s cular d isea se , retinal deg enerative di se ase(e.g., age -re l a ted maculardegenerati on,  Stargardt 's  di s eas e
rion itself._In comparison_to the DNA in_the nucleus_of_the cell_(nDNA),_mtDNA is easily_damaged by free_radicals and the ROS_that it produces._Freely_floating mtDNA lacks protective measures associated with nDNA, and therefore suffers from multiple mutations._It_has been_estimated_that_the lack of protective measures_results in mutations to mtDNA_occurring 10_to 20 times more frequently than mutations to_nDNA.
Mitochondrial_damage and/or dysfunction_contribute to various disease states. Some diseases are due_to mutations or deletions in the_mitochondrial genome. Mitochondria_divide_and_proliferate with a faster_turnover rate than their host cells,_and their replication is under control_of the nuclear genome. If a threshold_proportion of mitochondria in a cell_is defective, and if a_threshold proportion_of such cells within a_tissue have defective_mitochondria, symptoms_of tissue or_organ dysfunction can result. Practically any_tissue can be_affected, and a large variety of_symptoms_can be present,_depending_on_the extent_to which different_tissues_are involved.
A_fertilized_ovum might contain both normal and_genetically_defective mitochondria. The segregation of defective mitochondria_into different tissues during_division_of this ovum is_a stochastic process, as will_be the ratio of defective to_normal mitochondria_within a_given tissue or cell (although there can be positive or negative_selection for defective mitochondrial genomes during_mitochondrial turnover within cells)._Thus, a_variety_of different pathologic_phenotypes_can emerge_out of a particular point mutation in_mitochondrial DNA._Conversely, similar phenotypes can emerge from_mutations or deletions affecting_different_genes within mitochondrial DNA. Clinical symptoms_in congenital mitochondrial diseases often manifest_in postmitotic tissues with high_energy_demands_like brain, muscle, optic nerve,_and myocardium, but other tissues including_endocrine glands, liver,_gastrointestinal tract, kidney, and hematopoietic tissue are_also_involved, again depending in part on_the_segregation of mitochondria during development, and_on_the_dynamics of mitochondrial turnover over_time.
In addition to congenital disorders involving_inherited defective mitochondria, acquired mitochondrial damage and/or dysfunction contribute_to diseases, particularly_neurodegenerative disorders associated with aging_like_Parkinson's,_Alzheimer's, Huntington's Diseases. The incidence of somatic mutations in mitochondrial_DNA rises_exponentially with age;_and diminished respiratory chain activity is found universally in aging_people. Mitochondrial dysfunction is also implicated in_excitotoxic neuronal injury, such as that associated with seizures or ischemia.
Other_pathologies with etiology involving mitochondrial damage and/or dysfunction_include schizophrenia, bipolar disorder, dementia, epilepsy, stroke,_cardiovascular disease, retinal degenerative_disease_(e.g., age-related macular degeneration, Stargardt's disease