Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11206-10. doi: 10.1073/pnas.1200313109. Epub 2012 Jun 25.
Autophagy has been implicated in a number of physiological processes important for human heath and disease. Autophagy involves the formation of a double-membrane cytosolic vesicle, an autophagosome. Central to the formation of the autophagosome is the ubiquitin-like protein autophagy-related (Atg)8 (microtubule-associated protein 1 light chain 3/LC3 in mammalian cells). Following autophagy induction, Atg8 shows the greatest change in expression of any of the proteins required for autophagy. The magnitude of autophagy is, in part, controlled by the amount of Atg8; thus, controlling Atg8 protein levels is one potential mechanism for modulating autophagy activity. We have identified a negative regulator of ATG8 transcription, Ume6, which acts along with a histone deacetylase complex including Sin3 and Rpd3 to regulate Atg8 levels; deletion of any of these components leads to an increase in Atg8 and a concomitant increase in autophagic activity. A similar regulatory mechanism is present in mammalian cells, indicating that this process is highly conserved.
自噬在许多对人类健康和疾病至关重要的生理过程中都有涉及。自噬涉及形成一个双层膜胞质囊泡,即自噬体。自噬体形成的核心是泛素样蛋白自噬相关 (Atg)8(哺乳动物细胞中的微管相关蛋白 1 轻链 3/LC3)。在自噬诱导后,Atg8 的表达变化是所有自噬所需蛋白中最大的。自噬的程度部分受 Atg8 数量的控制;因此,控制 Atg8 蛋白水平是调节自噬活性的一种潜在机制。我们已经确定了 ATG8 转录的负调节剂 Ume6,它与包括 Sin3 和 Rpd3 在内的组蛋白去乙酰化酶复合物一起作用来调节 Atg8 水平;这些成分中的任何一个缺失都会导致 Atg8 的增加和自噬活性的相应增加。在哺乳动物细胞中存在类似的调节机制,表明该过程高度保守。