The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death.
The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death.
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DOI：
10.1016/j.devcel.2018.09.015
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发表时间：
2018-11-05
影响因子：
11.8
通讯作者：
Baehrecke EH
中科院分区：
文献类型：
--
作者：
Velentzas PD;Zhang L;Das G;Chang TK;Nelson C;Kobertz WR;Baehrecke EH
营养物质的可利用性影响细胞生长和存活所需物质的产生和降解。自噬是一种营养调节的过程，用于降解细胞质物质，并已与人类疾病。溶质转运蛋白影响营养物质的可用性和感知，但我们对转运蛋白如何影响自噬知之甚少。在这里，我们筛选的溶质转运所需的自噬依赖性细胞死亡，并确定CG 11665/爱马仕。我们发现，爱马仕是所需的类固醇触发的唾液腺细胞死亡和TNF诱导的非凋亡性眼细胞死亡的自噬。爱马仕编码质子偶联的单羧酸转运蛋白，其优先转运丙酮酸而不是乳酸。mTOR信号在爱马仕突变细胞中升高，并且mTOR功能降低抑制爱马仕唾液腺细胞死亡表型。爱马仕与人SLC 16 A11最为相似，后者是一种最近被发现与2型糖尿病有关的蛋白质，因此提供了丙酮酸、mTOR、自噬和可能的代谢紊乱之间的联系。Velentzas等人鉴定了在果蝇中与细胞死亡相关的自噬中对丙酮酸转运蛋白爱马仕的需要。爱马仕影响mTOR信号传导，并且与2型糖尿病相关的人类蛋白SLC 16 A11相似，从而表明自噬与代谢紊乱之间存在进一步的联系。
Nutrient availability influences the production and degradation of materials that are required for cell growth and survival. Autophagy is a nutrient-regulated process that is used to degrade cytoplasmic materials, and has been associated with human diseases. Solute transporters influence nutrient availability and sensing, yet we know little about how transporters influence autophagy. Here we screen for solute transporters that are required for autophagy-dependent cell death, and identify CG11665/hermes. We show that hermes is required for both autophagy during steroid-triggered salivary gland cell death and TNF-induced non-apoptotic eye cell death. hermes encodes a proton-coupled monocarboxylate transporter that preferentially transports pyruvate over lactate. mTOR signaling is elevated in hermes mutant cells, and decreased mTOR function suppresses the hermes salivary gland cell death phenotype. Hermes is most similar to human SLC16A11, a protein that was recently implicated in type 2 diabetes, thus providing a link between pyruvate, mTOR, autophagy and possibly metabolic disorders. Velentzas et al. identify a requirement for the pyruvate transporter Hermes in autophagy that is associated with cell death in Drosophila. Hermes influences mTOR signaling and is similar to the type 2 diabetes-associated human protein SLC16A11, thus suggesting a further link between autophagy and metabolic disorders.
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影响因子：
3.3
作者：
Hoffman NE;Chandramoorthy HC;Shanmughapriya S;Zhang XQ;Vallem S;Doonan PJ;Malliankaraman K;Guo S;Rajan S;Elrod JW;Koch WJ;Cheung JY;Madesh M
通讯作者：
Madesh M
影响因子：
10.5
作者：
Guo, Jessie Yanxiang;Chen, Hsin-Yi;White, Eileen
通讯作者：
White, Eileen
DOI：
10.1073/pnas.1312570111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Faubert, Brandon;Vincent, Emma E.;Jones, Russell G.
通讯作者：
Jones, Russell G.
影响因子：
9.8
作者：
Dumitrescu, AM;Liao, XH;Refetoff, S
通讯作者：
Refetoff, S
影响因子：
29
作者：
Ebato, Chie;Uchida, Toyoyoshi;Watada, Hirotaka
通讯作者：
Watada, Hirotaka