Uphononongo luchaza indlela yenoveli ebandakanyekayo ekuqhubekeni kwesifo sesibindi esinamafutha angasinxilisayo kwaye iqaqambisa iprotein iMitofusin 2 njengamandla okuba yimodeli yonyango enokwenzeka.
Isifo sesibindi esinamafutha angenatywala sesona sifo sixhaphakileyo sesibindi esichaphazela abantu abangaseli tywala okanye abangaseli tywala kangako. Sichaphazela ama-25 ekhulwini abantu behlabathi kwaye sixhaphake kakhulu kumazwe aphuhlileyo. Esi sifo sibonakala ngokuqokelelwa kwamafutha angaphezulu kwiiseli zesibindi okukhokelela kwiingxaki ezahlukeneyo zesibindi. Le meko kunzima ukuyifumanisa kwasekuqaleni. Akukho nyango lufumanekayo lwesifo sesibindi esinamafutha angenatywala kwaye oogqirha ngokubanzi bacebisa ukunciphisa umzimba. Kwisifo esibi esibizwa ngokuba yi-non-alcoholic steatohepatitis (NASH), ukuqokelelwa kwamafutha kuhamba nokudumba, ukufa kweeseli kunye ne -fibrosis.
Uphononongo olupapashwe kwiCell ngoMeyi 2, 2019 lucebisa indlela entsha yonyango enokwenzeka yokunyanga isifo sesibindi esinamafutha angenatywala . Abaphandi bafumanise iproteni ye-mitochondrial ebizwa ngokuba yiMitofusin 2 enokuba yenye yezinto ezinokukhusela kule meko. Kolu phando lwabo babone ukuba amanqanaba eproteni yeMitofusin 2 abonwa ephantsi kwizigulana ezine-NASH njengoko kubonwe kwiibhayoloji zesibindi sabo . Amanqanaba aphantsi ayekho nakwiinqanaba zokuqala ze-NASH nto leyo ebonisa ukuba esi sifo sikhula xa iproteni yeMitofusin 2 incipha kwiiseli zesibindi. Imeko efanayo ibonwe kwiiseli zesibindi zemodeli yegundane yesifo sesibindi esinamafutha angenatywala . Kwiimpuku ukwehla kwamanqanaba eMitofusin 2 kwakubangela ukudumba kwesibindi, imetabolism engaqhelekanga ye-lipid, i-fibrosis yesibindi 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.
Uvavanyo oluneenkcukacha lubonise ukuba iproteni ye-membrane iMitofusin 2 ibopha ngokuthe ngqo kwaye inceda ukudluliselwa kwe-phosphatidylserine (PS) eveliswa ikakhulu kwi-endoplasmic reticulum (ER). I-Mitofusin 2 ikhupha i-PS kwii-membranes ivumela ukudluliselwa kwe-PS kwi-mitochondria apho i-PS iguqulwa ibe yi-phosphatidylethanolamine (PE) ukuze ithunyelwe kwi-ER ukuze kwenziwe i-phosphatidylcholine. Ukunqongophala kwe-Mitofusin 2 kubangela ukuncipha kokudluliselwa kwe-PS ukusuka kwi-ER ukuya kwi-mitochondria okuphazamisa imetabolism ye-lipid. Olu dluliselo olunesiphako lukhokelela kuxinzelelo lwe-ER kwaye lubangela iimpawu ezifana ne-NASH kunye nomhlaza. Kwakucacile ukuba i-hepatic Mitofusin 2 iyancitshiswa kwisibindi somntu ngexesha lokuqhubela phambili ukusuka kwi-steatosis elula ukuya kwi-NASH. Olu phononongo luchaza umsebenzi omtsha we-Mitofusin 2 ekugcineni imetabolism ye-phospholipid. Unxibelelwano phakathi kwe-Mitofusin 2 kunye ne-phospholipids lubaluleke kakhulu kuba oku kunokuchaphazela ii-antioxidant, anti-inflammatory, anti-fibrotic properties kunye nemisebenzi emininzi exhomekeke kwi-membrane. Ukuphinda kuvele iMitofusin 2 kwiimpuku ezitya i-chow kuphucule isifo sesibindi.
Olu phononongo lwangoku luchaza indlela entsha engazange ixelwe ngaphambili yokuphuhliswa kwesifo sesibindi esinamafutha angenatywala kwaye lugxininisa iprotheyini yeMitofusin 2 njengeyona nto intsha inokwenzeka yokunyanga isifo sesibindi esinamafutha angenatywala . Izifundo zexesha elizayo ziya kugxila kwiindlela ezahlukeneyo ezinokuphucula amanqanaba eMitofusin 2 ngaphandle kokubangela iziphumo ebezingalindelekanga.
***
Umthombo (s)
UHernández-Alvarez MI. et al. 2019. Ukudluliselwa kwe-Endoplasmic Reticulum-Mitochondrial Phosphatidylserine okunqongopheleyo kubangela isifo sesibindi. Iseli, 177 (4). https://doi.org/10.1016/j.cell.2019.04.010
***
Amagqabantshintshi zivaliwe.