2013-JCB-Where is mTOR and what is it doing there?

Table 1 Lysosome localization of TORC1

Table 2. Localization of TORC1 to other organelles

This table groups the most important reports that link TORC1 and mTORC1 to sites apart from the lysosome. By using comparable techniques to those that revealed lysosomal localization of mTORC1 ( Table 1), distinct components of TORC1 have also been identified at other sites including the nucleus核 and mitochondria线粒体. ChIP, chromatin immunoprecipitation染色质免疫沉淀; PFA, paraformaldehyde多聚甲醛.

Figure 1 Localization of mTORC1 signaling

mTORC1 is in the cytoplasm细胞质 when amino acids levels are low. Addition of amino acids stimulates the recruitment of mTORC1 in a Rag-dependent manner to the lysosomal surface溶酶体表面.

Upon growth factor stimulation, PI3K produces PIP3 in the plasma血浆 membrane, which in turn activates PDK1 and Akt. After phosphorylation by PDK1, Akt phosphorylates and thereby inhibits the TSC complex, possibly at the lysosome 溶酶体and the peroxisome过氧物酶体. Reduced TSC complex GAP activity leads to an increase in GTP-bound Rheb. Rheb-GTP at the lysosomal溶酶体 surface directly binds to and activates mTORC1. Osmotic 渗透压stress induces sequestration 诱发封存of mTORC1 in stress granules. Pools of mTORC1 have also been reported at other sites, including mitochondria线粒体 and the nucleus原子核.

Figure 2 Localization of mTORC2 signaling

mTORC2 interacts with ribosomes核糖体 in a PI3K-dependent manner. Upon growth factor stimulation, mTORC2 is recruited to MAMs, presumably from the cytoplasm大概从细胞质中. mTORC2 has also been observed in the nucleus原子核 and on lipid rafts脂质阀 at the plasma membrane质膜.

Table 3. Mitochondria线粒体, ER, MAM, and other localization of mTORC2

This table groups the most important reports that investigate TORC2 and mTORC2 localization. mTORC2 has consistently been identified in proximity to 接近mitochondria, the ER, and MAM. Other studies suggest that mTORC2 is nuclear细胞核 or at the plasma血浆膜 membrane.
EM, electron microscopy电子显微镜学; PFA, paraformaldehyde.多聚甲醛