近日,，來(lái)自美國(guó)匹茲堡大學(xué)醫(yī)學(xué)中心的研究人員發(fā)現(xiàn),，c-Myc能夠短暫的控制線粒體的結(jié)構(gòu),、功能及動(dòng)力學(xué)變化,，相關(guān)研究成果于5月21日在線發(fā)表在PLoS ONE上,。
c-myc基因是myc基因家族的重要成員之一，它既是一種可易位基因,，又是一種可調(diào)節(jié)基因,，也是一種能夠使細(xì)胞無(wú)限增殖，獲得永生化功能,，并促進(jìn)細(xì)胞分裂的基因,。c-myc基因與多種腫瘤發(fā)生發(fā)展有關(guān)，其表達(dá)產(chǎn)物在調(diào)節(jié)細(xì)胞生長(zhǎng),、分化或惡性轉(zhuǎn)化中發(fā)揮重要作用,。
之前的研究就已經(jīng)發(fā)現(xiàn)，c-Myc (Myc)癌蛋白能夠控制粒線體的生物合成以及多種與氧化磷酸化(OXPHOS)有關(guān)的酶的功能，但是,，這些事件的潛在調(diào)節(jié)機(jī)制目前還不明確,。
J. Anthony Graves等人發(fā)現(xiàn)，在myc-/-纖維母細(xì)胞重表達(dá)Myc以后,，線粒體的數(shù)量會(huì)表現(xiàn)出逐漸累積的現(xiàn)象,，而且，膜極化以及線粒體融合也出現(xiàn)增加,。OXPHOS缺陷也被發(fā)現(xiàn)表現(xiàn)出一定程度的修復(fù)，雖然電子傳遞鏈復(fù)合體(ETC)里的結(jié)構(gòu)性異常還沒(méi)有被標(biāo)準(zhǔn)化,。
與之相反,，研究人員發(fā)現(xiàn)，下調(diào)Myc后會(huì)導(dǎo)致線粒體質(zhì)量（mass）逐漸下降,，線粒體融合很快減少,，而且膜電位也很快損失。
總的來(lái)說(shuō),，與線粒體的分裂及融合特異相關(guān)的蛋白的水平增加表明,，Myc通過(guò)影響這些過(guò)程，影響了線粒體的質(zhì)量,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0037699
PMC:
PMID:
Mitochondrial Structure, Function and Dynamics Are Temporally Controlled by c-Myc
J. Anthony Graves*, Yudong Wang, Sunder Sims-Lucas, Edward Cherok, Kristi Rothermund, Maria F. Branca, Jennifer Elster, Donna Beer-Stolz, Bennett Van Houten, Jerry Vockley, Edward V. Prochownik.
Although the c-Myc (Myc) oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS), the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored.We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion.A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC) are not entirely normalized.Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter.The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell.
