Uphononongo luchaza indlela yenoveli ebandakanyekayo ekuqhubekeni kwesifo sesibindi esinamafutha angasinxilisayo kwaye iqaqambisa iprotein iMitofusin 2 njengamandla okuba yimodeli yonyango enokwenzeka.
Ayinatywala amanqatha esibindi isifo sesona sixhaphakileyo isibindi imeko echaphazela abantu abangaseliyo utywala okanye utywala obuncinane kakhulu. Ichaphazela i-25 pesenti yabemi behlabathi kwaye ixhaphake kakhulu kumazwe ahambele phambili. Le meko ibonakaliswe ngokuqokelelwa kwamafutha angaphezulu kwiiseli ze-hepatic ezikhokelela kukungasebenzi kakuhle kwesibindi. Le meko kunzima ukuyifumanisa kwasekuqaleni. Alukho unyango olufumanekayo lwamafutha angengawo utywala isibindi isifo kwaye oogqirha ngokubanzi bancomela ukunciphisa umzimba. Kwimeko embi yesi sifo ebizwa ngokuba yi-non-alcoholic steatohepatitis (NASH), ukuqokelelwa kwamafutha kukhatshwa kukudumba, ukufa kweseli kunye i-fibrosis.
Uphando olupapashwe kwi iseli ngoMeyi 2, 2019 iphakamisa into entsha ekujoliswe kuyo yonyango enokunyanga amanqatha angengawo utywala. isifo sesibindi. Abaphandi baye bafumanisa iprotheni ye-mitochondrial ebizwa ngokuthi i-Mitofusin 2 enokuba yenye yezinto ezinokubonelela ngokhuseleko kule meko. Kuphononongo lwabo baye babona ukuba amanqanaba eprotein ye-Mitofusin 2 abonwa ephantsi kwizigulana eziphethwe yi-NASH njengoko zibonwa kwimpilo yazo. isibindi biopsy. Amanqanaba aphantsi ayekho nakwiinqanaba zokuqala ze-NASH ezibonisa ukuba esi sifo sikhula xa iprotheni ye-Mitofusin 2 iyancipha kwiiseli zesibindi. Imeko efanayo yabonwa kwiiseli ze-hepatic zemodeli ye mouse ye isibindi esinamafutha angasinxilisayo Isifo .Kwiimpuku ukuhla kwamanqanaba eMitofusin 2 kwakunoxanduva lokudumba kwesibindi, ukungahambi kakuhle kwe-lipid metabolism, isibindi i-fibrosis kunye nomhlaza wesibindi.
Kwiimvavanyo ezenziwe kwimodeli ye-mouse ye-NASH, iigundane zafakwa phantsi kwe-chow yokutya kwiiveki ze-2 kunye ne-adenoviruses encoding iprotheni ye-Mitofusin 2 yafakwa emithanjeni kwiigundane. Intsholongwane yatshintshwa ngokuthe ngqo ukuba iveze iiprotheyini. Izibindi zezi mpuku zahlaziywa emva kweveki ye-1. Iziphumo zibonise ukuba imeko ye-NASH yabonwa ukuba iphucule kwiimpuku ngokuphuculwa okubalulekileyo kwi-lipid metabolism.
Iimvavanyo ezinzulu zibonise ukuba iprotheni ye-membrane i-Mitofusin 2 ibophelela ngokuthe ngqo kwaye inceda ukuhanjiswa kwe-phosphatidylserine (PS) eyenziwa ngokuyinhloko kwi-endoplasmic reticulum (ER). I-Mitofusin i-2 ikhupha i-PS kwi-membrane evumela ukudluliselwa kwe-PS kwi-mitochondria apho i-PS iguqulwa ibe yi-phosphatidylethanolamine (PE) ukuba ithunyelwe kwi-ER yokwenza i-phosphatidylcholine. Ukusilela kwi-Mitofusin 2 kubangela ukunciphisa ukudluliselwa kwe-PS ukusuka kwi-ER ukuya kwi-mitochondria ephazamisa i-lipid metabolism. Olu dluliselo lunesiphako lukhokelela kuxinzelelo lwe-ER kwaye lubangela iimpawu ezinjenge-NASH kunye nomhlaza. Kwacaca ukuba i-Hepatic Mitofusin 2 iyancipha kwisibindi somntu ngexesha lokuqhubela phambili ukusuka kwi-steatosis elula ukuya kwi-NASH. Uphononongo luchaza umsebenzi omtsha weMitofusin 2 ekugcinweni kwe-phospholipid metabolism. Ikhonkco phakathi kwe-Mitofusin 2 kunye ne-phospholipids ibaluleke kakhulu kuba oku kunokuchaphazela i-antioxidant, i-anti-inflammatory, i-anti-fibrotic properties kunye nemisebenzi emininzi exhomekeke kwi-membrane. Ukubonakaliswa kwakhona kweMitofusin 2 kwiimpuku kwi-chow yokutya kuphuculwe isibindi isifo.
Uphononongo lwangoku luchaza inoveli ebingaxelwanga ngaphambili kwindlela yokuphuhliswa kwesifo sesibindi esinamafutha angasinxilisayo kwaye iqaqambisa iprotein ye-Mitofusin 2 njengento ekujoliswe kuyo yonyango entsha yokunyanga amanqatha angengotywala. isibindi isifo. Izifundo zexesha elizayo ziya kugxila kwiindlela ezahlukeneyo ezinokuphucula amanqanaba e-Mitofusin 2 ngaphandle kokubangela iziphumo ebezingalindelekanga.
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{Unokufunda iphepha lokuqala lophando ngokunqakraza ikhonkco le-DOI elinikwe ngezantsi kuluhlu lwemithombo ecatshulweyo (s)}
Umthombo (s)
UHernández-Alvarez MI. okqhubekayo. 2019. Ukungaphumeleli kwe-Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Ibangela isifo sesibindi. Iseli, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
