Ntu Ⅰ Lub Luag Haujlwm Ntawm Mitochondrial DNA Kev puas tsuaj hauv cov kab mob hauv lub raum: Lub Biomarker Tshiab

Abstract

Lub raum yog ib qho khoom noj uas muaj mitochondria, thiab cov kab mob hauv lub raum tau lees paub tias yog cov kab mob ntsig txog mitochondria. Intact mitochondrial DNA (mtDNA) tswj kev ua haujlwm ntawm mitochondrial. Mitochondrial dysfunction tshwm sim los ntawm mtDNA kev puas tsuaj, suav nrog kev cuam tshuam mtDNA replication, mtDNA hloov, mtDNA to, thiab mtDNA methylation, yog koom nrog hauv kev loj hlob ntawm cov kab mob hauv lub raum. Ntawm no, peb tshuaj xyuas lub luag haujlwm ntawm mtDNA kev puas tsuaj hauv ntau qhov chaw ntawm cov kab mob raum, suav nrog mob raum raug mob (AKI) thiab mob raum mob (CKD). Hauv ntau hom kab mob hauv lub raum, kev puas tsuaj mtDNA cuam tshuam nrog kev ua haujlwm tsis zoo ntawm lub raum. Qib ntawm mtDNA nyob rau hauv peripheral serum thiab zis kuj qhia txog cov xwm txheej ntawm lub raum raug mob. Alleviating mtDNA kev puas tsuaj tuaj yeem txhawb kev rov ua haujlwm ntawm mitochondrial los ntawm kev kho tshuaj exogenous thiab yog li txo cov mob raum. Hauv luv luv, peb txiav txim siab tias kev puas tsuaj mtDNA tuaj yeem ua tus tshiab biomarker rau kev ntsuas lub raum raug mob nyob rau hauv ntau yam ua rau lub raum tsis ua haujlwm, uas muab lub hauv paus tshiab rau kev cuam tshuam mtDNA raws li kev kho mob rau cov kab mob hauv lub raum.

Ntsiab lus

mitochondrial DNA; kab mob raum; mtDNA replication; mtDNA kev hloov pauv; mtDNA xau; mtDNA methylation.

Nyem qhov no kom tau txais txiaj ntsig ntawm Cistanche

Taw qhia

Lub raum tshem tawm cov khoom pov tseg metabolic los ntawm glomerular filtration barrier thiab tswj cov dej-electrolyte tshuav ntawm lub raum tubular reabsorption. Raws li lub cev muaj zog xav tau, lub raum muaj ntau mitochondria los tsim ATP los txhawb nqa nws cov homeostasis. Cov kev tshawb fawb ntau ntxiv tau qhia tias kev ua haujlwm tsis zoo ntawm mitochondrial ua lub luag haujlwm tseem ceeb hauv qhov tshwm sim thiab kev loj hlob ntawm cov kab mob raum, suav nrog mob raum raug mob (AKI) thiab mob raum mob (CKD) [1,2]. Txawm li cas los xij, cov txheej txheem ntawm mitochondrial tsis ua haujlwm tseem tsis tau txhais.

Mitochondrial DNA (mtDNA) yog ob-stranded ncig DNA uas yog ywj siab ntawm nuclear DNA. Feem ntau, mtDNA nrog qhov ntev ntawm 16,596 lub hauv paus khub yog nyob rau hauv mitochondrial matrix. mtDNA muaj nws tus kheej transcriptional thiab translational system thiab encodes 2 rRNAs, 22 tRNAs, thiab 13 polypeptides. Cov polypeptides no muaj xws li ND1-6, ND4L, COXI-III, cyt-b, ATPase6, thiab ATPase8, uas koom nrog hauv kev sib xyaw ntawm mitochondrial respiratory complexes kom muaj kev ncaj ncees ntawm cov saw hlau thauj hluav taws xob (ETC) thiab Kev ruaj ntseg ntawm oxidative phosphorylation (OXPHOS) [3]. Kev ua haujlwm ntawm OXPHOS muab lub zog xav tau ntawm lub cev rau cov hlwb thiab cov kabmob, thiab ETC yog lub hauv paus tseem ceeb ntawm cov pa oxygen reactive (ROS) ntau lawm. mtDNA kev puas tsuaj ua rau tsis muaj peev xwm mitochondrial muaj nuj nqi, xws li ROS overproduction, txo ATP tiam, thiab hloov metabolite profiles [4]. Kev puas tsuaj mtDNA tau nrog oxidative kev nyuaj siab ua kom thiab txo cov mitochondrial loj [5]. Qhov tseem ceeb, mtDNA kev ncaj ncees muaj feem cuam tshuam nrog kev ua haujlwm mitochondrial. Ntxiv nrog rau kev txiav txim siab mitochondrial muaj nuj nqi ncaj qha, mtDNA tuaj yeem ua raws li cov kab mob endogenous. Curiously, cov kev tshawb fawb tshiab tau tshaj tawm tias mtDNA xau mus rau hauv cytoplasm tuaj yeem ua tus neeg kho mob inflammatory thiab ua kom lub cev tiv thaiv kab mob inflammatory teb [6,7].

Cov txheej txheem ntawm DNA transcription thiab replication yog feem ntau nrog los ntawm kev hloov, deletions, insertions, translocations, thiab strand so. Cov kev puas tsuaj no tuaj yeem raug nthuav tawm sai sai los ntawm kev kho cov kab ke DNA nuclear los txhawb kev ncaj ncees genomic (8].

wevermtDNA yog tsis muaj kev paub txog kev puas tsuaj-sensing signaling thiab tiv thaiv histones. Kev tsim tawm ntau dhauROS cuam tshuam oxidative kev ntxhov siab hauv cov hlwb thiab tuaj yeem ua rau muaj kev hloov pauv mtDNA ntau dua, kev sib tsoo, thiab tshem tawm, tsim kom muaj lub voj voog tsis zoo ntawm mtDNA kev puas tsuaj (9] Yog li, nws yog qhov nkag siab ntau dua rau kev puas tsuaj los ntawm sab hauv thiab sab nrauv tsis zoo.

Lub luag haujlwm ntawm mtDNA kev puas tsuaj hauv ntau yam kab mob, xws li mob qog noj ntshav, kab mob plawv, kab mob siab, thiab kab mob hauv lub paj hlwb, tau nyiam ntau yam (10-13Ib yam li ntawd, nws tau tshaj tawm tias kev puas tsuaj mtDNA, suav nrog kev cuam tshuam mtDNA replicationmtDNA kev hloov pauv, mtDNA leakage, thiab kev hloov kho mtDNA, ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm cov kab mob raum (Daim duab 1).

Daim duab 1. Hom kev puas tsuaj mtDNA. mtDNA puas muaj xws li impaired mtDNA replication, mtDNA mutations, mtDNA to, thiab mtDNA methylation. mtDNA replication ua haujlwm nyob rau hauv ib qho kev txuag ib nrab thiab muaj ntau yam enzymes, xws li TWINKLE, Pol y, PORMT, andmtSSB, uas tuaj yeem cuam tshuam mtDNA replication thaum lawv cuam tshuam. Cov hom kev hloov pauv ntawm mtDNA suav nrog kev hloov pauv, hloov chaw, ntxig, thiab tshem tawm. Leaked mtDNA tuaj yeem hloov mus rau hauv cov ntshav ntshav thiab cov zis ntawm cov hlab ntsha thiab cov zis, raws li kev ua ntawm DNMls, cov tshuaj methyl pub dawb tau txais los ntawm SAM raug xa mus rau CpGislands los tsim 5'-methylcytosine. (OriH, lub hauv paus chiv keeb ntawm hnyav strand replication; OriL, lub hauv paus chiv keeb ntawm lub teeb strand replication; Pol y, polymerase gamma; PORMT, mitochondrial RNA polymerase; mtSSBmitochondrial ib leeg-strand binding protein; SAM, S-adenosyl-L-methionine; SAH, S-adenosyl-L.homocysteine; SAMC, S-adenosyl methionine cab kuj; DNMTs, thiab DNA methyltransferases).

Cistanche extract

Hom kev puas tsuaj mtDNA

1. Impaired mtDNA Replication

Kev ruaj ntseg ntawm mtDNA yog qhov tseem ceeb rau kev tswj hwm kev noj qab haus huv ntawm mitochondria hauv cov hlwb. mtDNA replication thiab faib nyob rau hauv mitochondrial networks ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa mitochondrial homeostasis. Zoo ib yam li nuclear DNA replication, mtDNA replication ua hauj lwm nyob rau hauv ib tug semi-conserved yam thiab entails ntau hom mechanisms, xws li strand-tsav thiab strand-coupled qauv [14]. Hauv txhua lub voj voog ntawm tes, mtDNA rov ua dua ntau zaus, thiab qhov rov ua dua ntawm ob txoj hlua, cov hlua hnyav, thiab lub teeb strand, tsis synchronized. mtDNA replication yog ze ze rau mitochondrial metabolism, thiab nws cov haujlwm yuav cuam tshuam los ntawm kev hloov pauv hauv cov mitochondrial metabolites, xws li nucleotides thiab NAD ntxiv. Interestingly, exogenous supplementation nrog NAD ntxiv rau precursor, beta-nicotinamide mononucleotide, nce lub pas dej ua ke ntawm mitochondrial nucleotides thiab txhawb mtDNA replication [15]. Kev txo qis mtDNA tus lej luam yog cuam tshuam nrog nce oxidative kev nyuaj siab los ntawm ROS overproduction, uas ntxiv ua rau mitochondria-txog metabolic ntshawv siab thiab apoptosis [16].

Ntau yam ntawm cov enzymes cuam tshuam thiab kev tswj hwm muaj feem cuam tshuam nrog mtDNA replication, xws li mtDNA polymerase (POL), mitochondrial single-strand binding protein (mtSSB), mitochondrial helicase TWINKLE, topoisomerase, thiab mitochondrial transcription factor A (TAM) [17,18] ]. Tag nrho cov xwm txheej no feem ntau yog encoded los ntawm cov noob caj noob ces. Yog li ntawd, mtDNA replication yog tswj los ntawm nws tus kheej thiab nuclear DNA. POL - cov hlwb tsis muaj kev cuam tshuam loj heev ntawm mtDNA, uas tau cawm los ntawm kev txhim kho mitochondrial deoxyribonucleoside triphosphate ntau lawm [19]. Activating transcription factor cuam tshuam nrog kev ntxhov siab 1 (ATFS-1) yog tsis nyob rau hauv noj qab haus huv mitochondria vim nws degradation los ntawm mtDNA-bound protease Lon peptidase 1 (LONP-1), tab sis nws accumulates nyob rau hauv puas mitochondria. LONP-1 inhibition nce ATFS{11}} thiab PLO khi rau mtDNA thiab txhawb nqa mtDNA replication li no txhim kho mtDNA heteroplasmy piv thiab rov kho OXPHOS [20]. mtSSB yog qhov tseem ceeb rau kev txwv tsis pub hloov pauv kev pib ua kom zoo dua RNA primer tsim ntawm ob lub hauv paus ntawm mtDNA replication thiab nws cov kev hloov pauv cuam tshuam rau mtDNA replication thiab induce mtDNA deletion [21,22]. TFAM deficiency ua rau qhov txo qis ntawm mtDNA tus lej luam thiab OXPHOS [23]. Hauv cov ntsiab lus, ua kom tiav mtDNA replication yog ib qho txheej txheem. Thaum ib qho ntawm cov kauj ruam no cuam tshuam, nws yuav ua rau muaj kev cuam tshuam mtDNA replication.

Standardized Cistanche

2. mtDNA Kev hloov pauv

mtDNA zoo nkaus li ntau zaus thiab raug rau kev hloov pauv ntau dua li cov DNA DNA. mtDNA kev hloov pauv feem ntau pom muaj nyob rau hauv cov kab mob hauv niam txiv, thiab qhov tsis zoo ib puag ncig kuj tuaj yeem ua rau muaj kev hloov pauv ntawm mtDNA [24]. Ob lub gene-coding cheeb tsam thiab lub voj hloov chaw (D-loop), uas ua lub luag haujlwm hauv kev tswj hwm kev hloov pauv, tuaj yeem hloov pauv hauv mtDNA, yog li cuam tshuam rau thaj chaw tseem ceeb ntawm genome.

Vim tias txhua lub mitochondrion muaj ntau qhov sib txawv ntawm cov ntawv luam mtDNA, hom mtDNA kev hloov pauv tuaj yeem muab faib ua homogeneous thiab heterogeneous mutations. Homogeneous mutations hais txog kev hloov pauv ntawm tag nrho cov mtDNA hauv mitochondria, whereas heterogeneous mutations xa mus rau kev sib koom ua ke ntawm mutant thiab qus-hom mtDNA. mtDNA kev hloov pauv muaj cov txiaj ntsig zoo ntawm kev ua haujlwm mitochondrial, ua rau muaj kev puas tsuaj ntawm lub zog ntawm tes [25]. Cov txiaj ntsig lom neeg ntawm kev hloov pauv yog nyob ntawm qhov kev faib ua feem ntawm mutant mtDNA thiab hom kev hloov pauv los ntawm cov hlwb. Yam tsawg kawg ntawm cov ntawv luam ntawm mtDNA kev hloov pauv uas ua rau muaj qhov tsis zoo hauv cov ntaub so ntswg thiab cov kabmob tshwj xeeb yog hu ua tus nqi pib, thiab qis dua tus nqi pib, qhov ntau dua qhov tshwm sim ntawm tus kabmob [26]. Qhov kev hloov pauv tus nqi muaj qhov cuam tshuam tseem ceeb rau kev kho mob tshwm sim ntawm lub zog dependence thiab tus kab mob thiab tus nqi pib sib txawv ntawm tus kheej cov ntaub so ntswg thiab lub cev.

Nrog rau kev txhim kho txuas ntxiv ntawm kev tshawb nrhiav thev naus laus zis, mtDNA cov kab mob cuam tshuam txog kev hloov pauv tau raug tshawb pom thiab tau txais kev nyiam ntawm cov kws tshawb fawb thiab cov kws kho mob. Cov kev tshawb fawb tau pom tias kev hloov pauv ntawm mtDNA cuam tshuam nrog kev loj hlob ntawm ntau yam kab mob, nrog rau cov kab mob plawv, kab mob raum, qog, thiab kev laus [27–30]. Tam sim no, tsis muaj kev kho mob zoo rau mtDNA cov kab mob cuam tshuam txog kev hloov pauv, uas feem ntau tsom rau kev txhim kho cov tsos mob. Yog li ntawd, nws yog ib qho tseem ceeb tshwj xeeb kom raug txheeb xyuas qhov chaw ntawm mtDNA kev hloov pauv.

Cistanche hmoov

3. mtDNA Leakage

Lub mitochondrial membrane zoo ib yam li cov cell membrane thiab muaj cov qauv bilayer los tswj kev ncaj ncees ntawm mitochondria. Lipids thiab cov proteins yog cov khoom tseem ceeb ntawm lub hauv paus mitochondrial membrane (IMM) thiab sab nraud mitochondrial membrane (OMM). Qhov sib txawv ntawm lawv cov muaj pes tsawg leeg txiav txim siab tias IMM thiab OMM muaj cov haujlwm sib txawv ntawm lub cev. OMM muaj ib tug loj tus naj npawb ntawm integral membrane proteins uas tswj mitochondrial permeability. Nyob rau hauv sib piv, lub IMM yog tsim los ntawm ntau yam carrier proteins thiab metabolism-txog enzymes uas yog lub luag hauj lwm rau complex mitochondrial biochemical tshua. Feem ntau, mtDNA yog encapsulated hauv mitochondrial matrix. Thaum cov txheej txheem kev ncaj ncees ntawm mitochondrial membrane raug cuam tshuam, mtDNA raug tso tawm rau hauv cytoplasm. Kev puas tsuaj mitochondrial membrane qauv thiab nce permeability yog qhov tseem ceeb ua rau mtDNA to. Hloov lipid muaj pes tsawg leeg nyob rau hauv mitochondrial membrane ua rau muaj zog mitochondrial permeability thiab mtDNA to [31]. Mitochondrial kev puas tsuaj los ntawm ntau yam yog feem ntau nrog los ntawm mtDNA to. Cov kev tshawb fawb tsis ntev los no tau qhia tias mtDNA tuaj yeem tso rau hauv cytoplasm los ntawm ntau txoj hauv kev, xws li BAK/BAX pore, voltage-dependent anion channel (VDAC) oligomer pore, thiab mitochondrial permeability transition pore (mPTP) [32–34], raws li qhia. hauv daim duab 2. Txawm li cas los xij, cov txheej txheem no tau kawm txog qhov tsis sib xws ntawm cov kab mob sib txawv.

Daim duab 2. mtDNA leakage induces inflammatory activation. mtDNA raug tso tawm rau hauv cytoplasm los ntawm ntau txoj hauv kev, xws li BAK / BAX pore, VDAC oligomer pore, thiab mPTP tDNA tso rau hauv cytoplasm activates inflammatory teb los ntawm ntau txoj kev taw qhia nrog rau cGAS-STING, TLR9, NLRP3, thiab AIM2 inflammasome. (cGAS, cyclic GMP-AMP synthase; STING, stimulator ntawm interferon genes; CGAMP, cyclic guanosine monophosphate-adenosinemonophosphate; p-TBK1, phospho-TANK-binding kinase-1; TLR9, tus xov tooj zoo li TRIF, 9; TIRdomain-muaj adapter-inducing IFN B; MyD88, myeloid diferentiation protein 88, NLRP3nod-zoo li receptor pyrin 3; ASC, apoptosis txuam speck zoo li protein; AlM2, tsis muaj nyob rau hauv melanoma2; VDAC, voltage-dependent anion channel; mPTP, mitochondrial perability pore?INFa, qog necrosis factor a; IL-6, interleukin-6; IL-18, interleukin-18; IL-1B, interleukin{{30} }B; NF-KB.nuclear factor kappa-B; p-IRF3, phospho-interferon regulatory factor-3; IFN, interferon).

Accumulated mtDNA in the cytoplasm is recognized as an endogenous pathogen and activates innate immune and inflammatory responses [12,35]. mtDNA released into the cytoplasm can activate inflammatory responses through multiple signaling pathways, including the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), toll-like receptor 9 (TLR9), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and absent in melanoma (AIM2) inflammasome signaling pathways [36]. cGAS is a member of the nucleotidyl transferase family and contains a DNA-binding region, which recognizes endogenous and exogenous DNA, including viral DNA, mtDNA, chromosomal terminal telomeric repeat sequence DNA, and cytoplasmic chromatin fragments. The recognition of DNA by cGAS is length-dependent, and DNA can effectively bind to cGAS when the length of dsDNA is >45 Ib. [37]. Lub pob txha phospholipase ntawm DNA khi rau cGAS nyob rau hauv ib qho kev tsis sib thooj-raws li thiab induces conformational hloov [38]. mtDNA tso rau hauv cytoplasm los yog peripheral ncig yog lees paub los ntawm cGAS thiab catalyzes tiam thib ob messenger cyclic guanosine monophosphate-adenosine monophosphate (cGMP), uas ntxiv activates STING-txog txoj kev, nrog rau hom 1 interferon (IFN) cov lus teb thiab cov classical. NF-κB inflammatory pathway, yog li ua kom lub cev tsis muaj zog [39]. TLR9 yog ib qho transmembrane protein feem ntau nyob rau hauv endoplasmic reticulum, uas muaj thaj tsam extracellular uas paub txog cov kab mob sib txuas nrog cov qauv molecular (PAMPs) thiab thaj tsam intracellular nrog rau tus xov tooj / interleukin -1 receptor (TIR) ​​qauv rau downstream signaling. TLR9 tuaj yeem ua raws li DNA lees paub receptor thiab koom nrog hauv lub cev tiv thaiv kab mob hauv tib neeg lub cev. Ntau cov kev tshawb fawb qhia tias TLR9 ua lub luag haujlwm tseem ceeb hauv kev txhim kho cov kab mob autoimmune [40,41]. TLR9 yog ib tug tswv cuab ntawm TLR tsev neeg ntawm cov proteins uas muaj feem xyuam nrog mtDNA [42]. mtDNA activates TLR9 thiab koom nrog hauv cytokine ntau lawm, splenic apoptosis, thiab raum raug mob hauv sepsis [43]. TLR9 kho qhov tsim ntawm cov lus teb inflammatory los ntawm kev ua kom NF-κB inflammatory pathway ntawm myeloid differentiation factor 88 (MyD88) [44]. NLRP3 activates caspase-1 thiab gastrin D (GSDMD), tso tawm ntau yam ntawm cov kab mob inflammatory thiab pib pyroptosis, hom tshiab ntawm kev tuag ntawm tes [45]. NLRP3 tuaj yeem lees paub ob qho tib si PAMPs thiab kev phom sij cuam tshuam nrog cov qauv molecular (DAMPs), thiab qhib NLRP3 inflammasome, uas muaj NLRP3 receptor protein, apoptosis-associated speck-like protein (ASC), thiab caspase-1 precursor protein (pro- caspase-1). Ib txoj kev tshawb fawb tsis ntev los no tau pom tias mtDNA nkag mus rau hauv cytoplasm qhib NLRP3 inflammasome hauv cov ntaub so ntswg adipose xim av, uas koom nrog kev rog-induced insulin tsis kam thiab impaired thermogenesis [46]. Qhov ob-stranded DNA receptor AIM2 kuj paub txog mtDNA tso tawm los ntawm BAK/BAX qhov pores thiab ua rau IL-1 zais cia thiab pyroptosis [47].

Cistanche tubulosa

4. mtDNA Methylation

DNA methylation yog ib qho ntawm cov kev tshawb fawb ntau tshaj plaws ntawm epigenetic mechanisms. Raws li qhov kev txiav txim ntawm DNA methyltransferases (DNMTs), methyl donor compounds muab tau los ntawm S-adenosylmethionine (SAM) raug xa mus rau CpG Islands tuaj ua 50 -methylcytosine (50 -mC), uas yog hom ntau tshaj plaws. DNA methylation. DMNTs suav nrog ob pawg loj, DNMT3a thiab DNMT3b, uas ua rau lub de novo methylation ntawm unmethylated DNA duplexes, thiab DNMT1, uas tswj lub xeev methylation ntawm DNA tom qab ib nrab kev txuag replication. Nws tau tshaj tawm tias DNMTs ua lub luag haujlwm tseem ceeb hauv kev tswj hwm tricarboxylic acid metabolites, mitochondrial ua pa, thiab oxidative stress [48,49].

Cov kev tshawb fawb tsis ntev los no tau qhia tias mtDNA kuj tseem tuaj yeem ua methylated thiab methylated mtDNA cuam tshuam txog kev kis kab mob [50]. Cov theem ntawm mtDNA methylation tuaj yeem cuam tshuam los ntawm ntau yam intracellular lossis extracellular yam. Qhov txawv txav tseem ceeb hauv mtDNA methylation tshwm sim hauv ntau yam kab mob, tshwj xeeb tshaj yog nyob rau hauv cov kab mob mitochondria [51]. Methylation ntawm mitochondrial genome tuaj yeem ua rau etiology ntawm tib neeg cov kab mob thiab hloov pauv methylation qib ntawm mtDNA raug soj ntsuam hauv cov qauv tsiaj thiab tib neeg cov ntaub so ntswg los ntawm cov neeg mob rog, ntshav qab zib, mob qog noj ntshav, thiab kab mob plawv thiab neurodegenerative [14]. Hypermethylation ntawm mtDNA noob kuj ua rau cov kab mob insulin tsis kam thiab muaj feem cuam tshuam txog kev mob metabolic [52].

mtDNA methylation yog ib qho tshwm sim thiab nkag siab tsis tiav uas tswj kev ua haujlwm mitochondrial. mtDNA methylation drifts ntawm qhov chaw sib txawv ntawm coding gene loci uas ua rau txo qis mtDNA tus lej luam thiab hloov cov noob qhia [53]. Qib ntawm mtDNA methylation tau cuam tshuam tsis zoo nrog mtDNA cov ntsiab lus [54]. mtDNA methylation tuaj yeem suav hais tias yog ib qho kev tshwm sim thaum ntxov thiab muaj peev xwm biomarker rau kev kwv yees kab mob zoo thiab kev kuaj mob. mtDNA methylation yog kev hloov pauv hloov pauv hloov pauv hloov pauv, ua rau nws yog lub hom phiaj kho mob tseem ceeb. Gene kho ntawm mtDNA methylation tseem nyob rau hauv kev tshawb fawb theem pib thiab kev kho mob thaum ntxov thiab, xws li, teeb meem kev nyab xeeb tsis tuaj yeem tsis quav ntsej. Nws vam tias kev txhim kho ntawm mitochondrial noob kho tshuab yuav pab peb kom nkag siab ntxiv tias mtDNA yog methylated li cas.

Cov ntaub ntawv

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Jun Feng 1,2, Zhaowei Chen 1,2, †, Wei Liang 1,2, Zhongping Wei 1,2 thiab Guohua Ding 1,2,

1 Division of Nephrology, Renmin Tsev Kho Mob ntawm Wuhan University, Wuhan 430060, Suav

2 Nephrology thiab Urology Research Institute ntawm Wuhan University, Wuhan 430060, Suav