MOTS-c 40mg

▎ Enzimba ya MOTS-c

▎ MOTS-c Okunoonyereza

Ensibuko y’okunoonyereza eya MOTS-c eri etya?

Mitochondria, ezikola nga 'powerhouse' y'obutoffaali, zikola kinene nnyo mu kukuuma homeostasis y'obutoffaali. Enkola z’empuliziganya wakati wa mitochondria ne nucleus zibadde zisinga kutunuulirwa mu kunoonyereza kwa ssaayansi okuva edda. Mitochondria zirina ensengekera y’obutonde (genome) eyetongodde. Okusukka obuzaale 37 obwa kalasi, okunoonyereza okwakakolebwa kulaga nti DNA ya mitochondrial nayo ekola enkodi ya peptides ennyimpi ezikola mu biramu, emu ku zo ye peptide evudde mu mitochondrial MOTS-c, ewandiikiddwa ekitundu kya mitochondrial 12S rRNA. Okuzuula kuno kugaziya nnyo obuwanvu bw’obuzaale bwa mitochondrial, nga kuwa endowooza empya ey’okunnyonnyola enkola enkulu ez’ebiramu nga empuliziganya ya mitochondrial-nuclear n’okulungamya enkyukakyuka mu mubiri.

Mu kiseera kino, obujjanjabi bw’endwadde nnyingi ezisomooza nga ssukaali n’obulwadde bw’ekibumba B obutawona bwolekedde ebizibu ebinene. Omulimu omukulu MOTS-c gw’ekola mu kulungamya enkyukakyuka y’ebinywa by’amagumba, gamba ng’okutumbula enkyukakyuka ya glucose, gulaga obusobozi bwayo mu kujjanjaba obuzibu mu nkyukakyuka y’emmere. Ekirala.

Enkola y’okukola ku MOTS-c eri etya?

Okulungamya Amakubo g’obubonero agakwatagana n’enkyukakyuka y’ebirungo

Okukola ekkubo ly’obubonero bwa AICAR-AMPK: MOTS-c ekola ekkubo ly’obubonero bwa AICAR-AMPK nga etaataaganya enzirukanya ya folate-methionine mu butoffaali. AMPK ekola etereeza enkyukakyuka y’amasoboza g’obutoffaali, gamba ng’okutumbula okutwalibwa kwa glucose n’okukyusa asidi w’amasavu. Mu nkyukakyuka ya glucose, kyongera okutambuza glucose transporter GLUT4 okudda mu luwuzi lw’obutoffaali, bwe kityo ne kyongera ku busobozi bw’obutoffaali okutwala glucose, okulongoosa obuziyiza insulini, n’okuyamba mu kuziyiza n’okujjanjaba endwadde z’enkyukakyuka mu mubiri nga sukaali ow’ekika eky’okubiri ^[1]..

Ebikosa amakubo amalala: Okusukka ekkubo lya AMPK, MOTS-c era ekola ku kkubo lya AKT, ekkubo lya oxidative stress, n’amakubo agakwatagana n’okuzimba. Ku bikwata ku kkubo lya AKT, liyinza okukwata ku nkola z’obutoffaali nga okukula, okukula, n’okuwangaala nga lifuga emirimu gy’ekkubo. Mu kkubo ly’okunyigirizibwa okw’okwokya, MOTS-C ekendeeza ku miwendo gy’okunyigirizibwa okw’okwokya mu butoffaali, ekendeeza ku kukola ebika bya okisigyeni ebikola (ROS), era ekuuma obutoffaali okuva mu kwonooneka kw’okwokya. Mu makubo agakwatagana n’okuzimba, kiziyiza okufuluma kw’abatabaganya okuzimba era kikendeeza ku kuddamu kw’okuzimba. Okugeza, mu bikolwa by’obulumi bw’okuzimba, MOTS-C ekendeeza ku kufulumya omutabaganya w’okuzimba mu jjembe ly’omugongo, bwe kityo n’etereeza obubonero bw’obulumi ^[2]..

Ekifaananyi 1 Emirimu emikulu egy’omubiri egya MOTS-C mulimu okukendeeza ku buziyiza bwa insulini, okuziyiza omugejjo, okulongoosa enkola y’ebinywa, okutumbula enkyukakyuka y’amagumba, okutumbula okulungamya abaserikale b’omubiri, n’okulwawo okukaddiwa ^[1]..

Okulungamya Okwolesebwa kw’Obuzaale

Okulungamya okwolesebwa kw’obuzaale bwa nyukiliya: Obutoffaali bwe busisinkana okunyigirizibwa kw’enkyukakyuka y’emmere, gamba ng’okuziyiza glucose n’okunyigirizibwa okw’okwokya, MOTS-C ekyuka n’egenda mu nyukiliya okulung’amya butereevu okwolesebwa kw’obuzaale bwa nyukiliya obukwatagana, bwe kityo ne kitumbula homeostasis mu butoffaali. Okugeza, MOTS-C ekyusakyusa okwolesebwa kw’obuzaale obukwatagana n’enkyukakyuka y’emmere nga GLUT4, STAT3, ne IL-10, n’ekwata ku nkola z’omubiri omuli enkyukakyuka ya glucose n’okulungamya abaserikale b’omubiri. Okwongera kw’okwolesebwa kwa GLUT4 kwongera ku kutwalibwa kwa glucose mu butoffaali; STAT3 yeetaba mu kukula kw’obutoffaali, okwawukana, n’okulungamya abaserikale b’omubiri; IL-10, ekirungo ekiziyiza okuzimba, kikendeeza ku kuddamu kw’okuzimba nga okwolesebwa kwayo kuli waggulu ^[1,3]..

Okwongera ku nkyukakyuka y’amasoboza

Enhanced Glycolysis: Mu bikolwa by’endwadde ez’enjawulo, nga enkola y’obuvune bw’amawuggwe-reperfusion injury (LIRI) evudde ku cardiopulmonary bypass (CPB), MOTS-c pretreatment eyongera ku glycolytic flux mu pulmonary microvascular endothelial cells (PMVECs). Kikendeeza ku buvune bwa LIRI nga kizzaawo homeostasis y’amaanyi g’obutoffaali n’okukendeeza ku lipid peroxidation okuyita mu upregulating key glycolytic enzyme PFKFB3. Kino kiraga nti MOTS-c ekyusa ekkubo lya glycolytic okusobola okuwa amaanyi agamala eri obutoffaali wansi w’okunyigirizibwa, bwe kityo ne kikuuma enkola y’obutoffaali eya bulijjo ^[4]..

Ebiva mu Kukuuma Obutoffaali

Okukendeeza ku kwonooneka kw’obutoffaali bw’omubiri (mitochondrial Damage): Mu nkola ya radiation pneumonitis (RP), MOTS-c yakendeeza nnyo ku buvune bw’ebitundu by’amawuggwe, okuzimba, n’okunyigirizibwa okw’okwokya ate ng’ezzaawo okufa kw’obutoffaali bw’omubiri (alveolar epithelial cell apoptosis) n’okwonooneka kw’obutoffaali bw’omubiri (mitochondrial damage). Enkola eno erimu okwongera ku miwendo gya nuclear factor E2-related factor 2 (Nrf2) n’okutumbula enkyukakyuka yaayo eya nuclear. Nrf2 ekola omuddirirwa gw’obuzaale obuziyiza obuwuka obuleeta obulwadde n’okukuuma obutoffaali, okukuuma enkola ya mitochondria. Kino kiraga nti MOTS-c ekuuma ebitundu ebyonooneddwa nga ekuuma mitochondria n’okukendeeza ku apoptosis ^[5]..

Okukuuma Obutoffaali Obulala: Mu kunoonyereza ku bulwadde bwa Duchenne muscular dystrophy (DMD), MOTS-c yazuulibwa nti erina eby’obugagga ebigenderera ebinywa eby’omunda. Kyongera ku glycolytic flux n’obusobozi bw’okufulumya amaanyi mu binywa ebizibu, ekiyamba okulongoosa enkola y’ebinywa. Ate era, mu bikolwa by’obulumi bw’okuzimba, MOTS-c eweebwa wakati oba ku bbali ekendeeza ku bulumi obuyitiridde nga eziyiza okuddamu kw’okuzimba n’okucamuka ennyo kw’obusimu, nga egaba ebikolwa eby’okukuuma obusimu ^[2,6]..

Enkola za MOTS-c ze ziruwa?

Obujjanjabi bw’obuzibu bw’enkyukakyuka mu mubiri:

Okulongoosa obuziyiza bwa insulini n’okuziyiza ssukaali: MOTS-c eyongera ku buziyiza bwa insulini, ekintu ekikulu ennyo mu kuziyiza sukaali ow’ekika eky’okubiri. Obuziyiza insulini kye kikulu mu kutandika obulwadde bwa sukaali obw’ekika eky’okubiri. MOTS-c eyinza okulongoosa okuwuliziganya kwa insulini ng’ekola ekkubo ly’obubonero erya AICAR-AMPK n’okulungamya enzirukanya ya folate-methionine mu butoffaali. Okunoonyereza okwakolebwa Gao Y kulaga nti kitumbula okutwala n’okukozesa glucose mu binywa by’amagumba, okufaananako okuggulawo amakubo amalala ag’okunyiga glucose mu butoffaali, bwe kityo ne kikendeeza ku mutindo gwa glucose mu musaayi ^[1]..

Okulungamya enkyukakyuka y’amasavu n’okulwanyisa omugejjo: Ku bikwata ku nkyukakyuka y’amasavu, MOTS-c eyongera ku thermogenesis y’amasavu aga kitaka era etumbula okufuuka kw’amasavu amazungu. Amasavu ga kitaka ganywa amaanyi nga gayita mu thermogenesis, ate amasavu amazungu aga browning kitegeeza okukyusa amasavu amazungu agatereka amaanyi okufuuka amasavu ga kitaka aganywa amaanyi. Enkola eno eyamba omubiri okumanyiira ennyonta era ekisinga obukulu, eziyiza omugejjo n’obuzibu mu kukyusakyusa amasavu, n’ewa amagezi amapya ku kuziyiza n’okujjanjaba omugejjo ^[1]..

Okuziyiza n’okujjanjaba endwadde ezeekuusa ku binywa:

Okutumbula enjawulo mu binywa: Okunoonyereza mu vitro kulaga nti peptide ey’ekika ky’omu nsiko MOTS-c eyongera ku kutondebwa kwa myotubular mu butoffaali bwa jjajja w’ebinywa by’omuntu (LHCN-M2) ne mouse (C2C12), so nga Y8F mutant peptide terina kikolwa kino. Okunoonyereza okulala kwalaga nti MOTS-c eyongera ku myotubulogenesis nga ekwatagana n’ekkubo lya IL-6/Janus kinase/signal transducer ne activator of transcription 3 (STAT3), bwe kityo ne kikendeeza ku STAT3 transcriptional activity ^[7]..

Okuziyiza okuzimba ebinywa: Emiwendo gya MOTS-c mu plasma gikwatagana bubi n’emiwendo gya myostatin. MOTS-c eziyiza palmitate-induced myotube atrophy mu differentiated C2C12 cells era ekendeeza ku plasma myostatin levels mu mbeba omugejjo induced endya. Kiziyiza okukendeera kw’ebinywa nga kyongera ku AKT phosphorylation, okuziyiza emirimu gya FOXO1 —ensonga y’okuwandiika waggulu eya myostatin n’obuzaale obulala obw’okukendeera kw’ebinywa —ate nga kitereeza emirimu gya mTORC2 ne PTEN n’okwongera ku mirimu gya CK2 okunyigiriza PTEN ^[8]..

Ebikolwa ebiziyiza okukaddiwa: Enkyukakyuka mu kwolesebwa kwa MOTS-c zikwatagana nnyo n’okukaddiwa, era eraga eby’obugagga ebiziyiza okukaddiwa. Kino kituukibwako okuyita mu nkola eziwera, omuli okulongoosa enkyukakyuka ya glucose ne lipid, okutumbula enkola ya mitochondrial y’obutoffaali, n’okukendeeza ku kuzimba okutambula obutawona mu nkola. Okunoonyereza okwakolebwa Gao Y et al. kiraga nti okulongoosa mu nkyukakyuka y’emmere kiwa obutoffaali amaanyi amangi era agatebenkedde. Okwongera ku nkola ya mitochondria kifaananako n'okulongoosa 'ekkolero ly'amaanyi,' ly'obutoffaali ate okukendeeza ku kuddamu kw'okuzimba kikendeeza ku kwonooneka kw'okuzimba kw'obutoffaali ^{[1] .}.

Mu bufunzi

Nga peptide evudde mu mitochondrial, MOTS-c ekola amakubo agalaga obubonero nga AMPK okulungamya enkyukakyuka ya glucose n’amasavu, okutumbula okukyusa amasavu amazungu okudda mu kitaka, n’okulongoosa okuziyiza insulini n’omugejjo, nga kiwa endagiriro empya ez’obujjanjabi eri obuzibu mu nkyukakyuka y’emmere. Kyongera ku njawulo y’amagumba, kinyigiriza okutondebwa kw’amagumba, kitebenkeza enkyukakyuka y’amagumba, era kiwagira okukuuma obulamu bw’amagumba. Kitereeza enjawulo y’ebinywa n’okuziyiza okuzimba, nga kikwata obusobozi bw’okuyingira mu nsonga mu buzibu obukwatagana n’ebinywa. MOTS-c eraga enkolagana ey’amaanyi ekwatagana n’okukola dduyiro: dduyiro upregulates okwolesebwa kwayo, era atabaganya emigaso gy’obulamu egy’okukola dduyiro. MOTS-c era ekola kinene mu kulwawo okukaddiwa n’enkola ezikwatagana nabyo.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Ning Ran munoonyereza alina akakwate n’ettendekero lya Carlson College of Veterinary Medicine mu Oregon State University. Omulimu gwe ogw’okusoma gukwata ku molekyu n’obusawo bw’okuvvuunula, ng’essira aliteeka ku bukodyo bw’okujjanjaba endwadde z’obusimu. Ran abadde omu ku bawandiisi ebitabo bingi mu bitabo ebikebereddwa banne, ekiyamba mu kutegeera enkola ya molekyu mu bikolwa by’endwadde. Ebintu by’anoonyerezaako mulimu okukola n’okukozesa peptide-conjugated oligonucleotides, wamu n’okunoonyereza ku busobozi bw’obujjanjabi bwa peptides ezisibuka mu mitochondrial. Ning Ran awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [6].

▎ Ebiwandiiko Ebikwatagana

[1] Gao Y, Wei X, Wei P, n’abalala. MOTS-c Eziyiza Mu Mirimu Obuzibu mu Nkyukakyuka y’Emibiri. Ebirungo ebikyukakyuka mu mubiri 2023; 13(1).DOI: 10.3390/metabo13010125.

[2] Wang Z, Yang L, Xu L, Liao J, Lu P, Jiang J. Enkola ey’omu makkati n’ey’okumpi eya MOTS-c ekendeeza ku bulumi obuyitiridde mu nkola y’ebibe ey’obulumi obuzimba. Okunoonyereza ku busimu 2024; 46 (2): 165-177.DOI: 10.1080/01616412.2023.2258584.

[3] Benayoun BA, Lee C. MOTS-c: Ekirungo ekitereeza enkodi mu mitochondrial ekya Nucleus. Ebiwandiiko ebikwata ku bulamu bw’omuntu 2019; 41 (9): e1900046.DOI: 10.1002/bies.201900046.

[4] Shen Z, Lu P, Jin W, n’abalala. MOTS-c Etumbula Glycolysis ng’eyita mu kkubo lya AMPK-HIF-1α-PFKFB3 Okutereeza Obuvune bw’Amawuggwe obuva ku CPB. American Journal of Obutoffaali bw’okussa n’obulamu bwa molekyu 2025. 10.1165/rcmb.2024-0533OC.

[5] Zhang Y, Huang J, Zhang Y, n’abalala. Peptide MOTS-c Eva mu Mitochondrial Ekendeeza ku Radiation Pneumonitis ng’eyita mu Nrf2-Dependent Mechanism. Ebirungo ebiziyiza obuwuka obuleeta obulwadde 2024; 13. https://api.semanticscholar.org/CorpusID:269876125. Enkola y’okukuuma obutonde bw’ensi.

[6] Ran N, Lin C, Leng L, n’abalala. MOTS-c etumbula okutwalibwa kwa phosphorodiamidate morpholino oligomer n’obulungi mu mbeba ezirina obulwadde bwa dystrophic. Embo Eddagala lya Molekyulu 2021; 13(2): e12993.DOI: 10.15252/emmm.202012993.

[7] García-Benlloch S, Revert-Ros F, Blesa JR, Alis R. MOTS-c etumbula enjawulo y’ebinywa mu vitro. Ebirungo ebiyitibwa Peptides 2022; 155: 170840.DOI: 10.1016/j.peptides.2022.170840.

[8] Kumagai H, Coelho A. R., Wan J., n’abalala. MOTS-c ekendeeza ku bubonero bwa myostatin n’okukendeera kw’ebinywa. American Journal of Physiology-Endocrinology n’enkyukakyuka mu mubiri 2021; 320(4): E680-E690.DOI: 10.1152/ajpendo.00275.2020.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.