Life Sciences Institute, and the Department of Molecular, Cellular and Developmental Biology, University of Michigan , Ann Arbor , MI , USA.
Autophagy. 2019 Oct;15(10):1838-1839. doi: 10.1080/15548627.2019.1621632. Epub 2019 Jun 11.
Macroautophagy/autophagy activity is carefully modulated to allow cells to adapt to changing environmental conditions and maintain energy homeostasis. This control notably occurs in part through the regulation of autophagy-related () gene expression. Others and we have jointly shown that under nutrient-rich conditions Dhh1 mediates the degradation of certain mRNAs, most significantly that of , through a Dcp2-dependent decapping pathway to maintain gene expression and autophagy activity at a basal level. More recently, we illustrated that under nitrogen-starvation conditions Dhh1 switches its role to become a positive regulator of autophagy, and promotes the translation of and mRNAs to meet the increased demand for autophagy activity. This regulation helps selected mRNAs to escape the general repression in translation that occurs when nutrients are limited and TOR is inhibited. Our studies also suggest that Dhh1's nutrient-dependent bidirectional regulation of auto-phagy is conserved in more complex eukaryotes. ATG: autophagy related; EIF4EBP: EIF4E binding protein; UTR: untranslated region.
自噬活性受到精细调控，以允许细胞适应不断变化的环境条件并维持能量稳态。这种调控部分是通过调控自噬相关基因的表达来实现的。我们和其他人共同表明，在营养丰富的条件下，Dhh1 通过依赖 Dcp2 的去帽途径介导某些 mRNAs（尤其是）的降解，以维持基因表达和自噬活性处于基础水平。最近，我们阐明了在氮饥饿条件下，Dhh1 转变为自噬的正调控因子，并促进和 mRNAs 的翻译，以满足自噬活性增加的需求。这种调控有助于特定的 mRNAs 逃避当营养物质有限和 TOR 受到抑制时发生的翻译普遍抑制。我们的研究还表明，Dhh1 对自噬的营养依赖性双向调控在更复杂的真核生物中是保守的。ATG：自噬相关；EIF4EBP：EIF4E 结合蛋白；UTR：非翻译区。
