The oncometabolite L-2-hydroxyglutarate is a common product of dipteran larval development.
The oncometabolite L-2-hydroxyglutarate is a common product of dipteran larval development.
复制标题
DOI：
10.1016/j.ibmb.2020.103493
复制
发表时间：
2020-12
影响因子：
3.8
通讯作者：
Tennessen JM
中科院分区：
文献类型：
--
作者：
Mahmoudzadeh NH;Fitt AJ;Schwab DB;Martenis WE;Nease LM;Owings CG;Brinkley GJ;Li H;Karty JA;Sudarshan S;Hardy RW;Moczek AP;Picard CJ;Tennessen JM
癌代谢物L-2-羟基戊二酸（L-2 HG）被认为是中心碳代谢的异常产物，能够破坏染色质结构、线粒体代谢和细胞分化。在大多数情况下，哺乳动物组织容易处置这种化合物，因为异常的L-2 HG积累诱导神经代谢紊乱并促进肾细胞癌。有趣的是，最近发现果蝇幼虫在正常生长条件下积累高水平的L-2 HG，提高了L-2 HG在昆虫代谢中发挥独特作用的可能性。在这里，我们探讨这一假设，通过分析L-2 HG水平在18种昆虫。而L-2 HG在大多数物种中处于低至中等水平（<100 pmol/mg;与小鼠肝脏相当），双翅目幼虫表现出积累高L-2 HG浓度的趋势（>100 pmol/mg），与埃及伊蚊、王蝇、和三种代表性的果蝇物种，其浓度超过1 nmol/mg -水平与在不能降解L-2 HG的突变小鼠中测量的水平相当。总的来说，我们的研究结果表明，地球上最大的动物群体之一通常在幼年生长期间产生高浓度的癌代谢物，暗示L-2 HG在双翅目发育进化中的作用，并提高了L-2 HG代谢可能有针对性地限制关键疾病媒介和农业害虫的生长的可能性。
The oncometabolite L-2-hydroxyglutarate (L-2HG) is considered an abnormal product of central carbon metabolism that is capable of disrupting chromatin architecture, mitochondrial metabolism, and cellular differentiation. Under most circumstances, mammalian tissues readily dispose of this compound, as aberrant L-2HG accumulation induces neurometabolic disorders and promotes renal cell carcinomas. Intriguingly, Drosophila melanogaster larvae were recently found to accumulate high L-2HG levels under normal growth conditions, raising the possibility that L-2HG plays a unique role in insect metabolism. Here we explore this hypothesis by analyzing L-2HG levels in 18 insect species. While L-2HG was present at low-to-moderate levels in most of these species (<100 pmol/mg; comparable to mouse liver), dipteran larvae exhibited a tendency to accumulate high L-2HG concentrations (>100 pmol/mg), with the mosquito Aedes aegypti, the blow fly Phormia regina, and three representative Drosophila species harboring concentrations that exceed 1 nmol/mg - levels comparable to those measured in mutant mice that are unable to degrade L-2HG. Overall, our findings suggest that one of the largest groups of animals on earth commonly generate high concentrations of an oncometabolite during juvenile growth, hint at a role for L-2HG in the evolution of dipteran development, and raise the possibility that L-2HG metabolism could be targeted to restrict the growth of key disease vectors and agricultural pests.
登录
查看更多内容
影响因子：
3.7
作者：
Callier V;Nijhout HF
通讯作者：
Nijhout HF
DOI：
10.1073/pnas.1614102114
发表时间：
2017-02-07
影响因子：
11.1
作者：
Li, Hongde;Chawla, Geetanjali;Tennessen, Jason M.
通讯作者：
Tennessen, Jason M.
缺氧介导的 L-2-羟基戊二酸增加可协调对还原应激的代谢反应。
影响因子：
29
作者：
Oldham WM;Clish CB;Yang Y;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
8.8
作者：
Mullen AR;Hu Z;Shi X;Jiang L;Boroughs LK;Kovacs Z;Boriack R;Rakheja D;Sullivan LB;Linehan WM;Chandel NS;DeBerardinis RJ
通讯作者：
DeBerardinis RJ
影响因子：
1.2
作者：
Li, Hongde;Tennessen, Jason M.
通讯作者：
Tennessen, Jason M.