Laboratory of Behavioral and Developmental Genetics, KU Leuven, Leuven, Belgium.
Autophagy. 2012 Sep;8(9):1401-3. doi: 10.4161/auto.21052. Epub 2012 Aug 13.
Autophagy plays an important role in cellular survival by resupplying cells with nutrients during starvation or by clearing misfolded proteins and damaged organelles and thereby preventing degenerative diseases. Conversely, the autophagic process is also recognized as a cellular death mechanism. The circumstances that determine whether autophagy has a beneficial or a detrimental role in cellular survival are currently unclear. We recently showed that autophagy induction is detrimental in neurons that lack a functional AMPK enzyme (AMP-activated protein kinase) and that suffer from severe metabolic stress. We further demonstrated that autophagy and AMPK are interconnected in a negative feedback loop that prevents excessive and destructive stimulation of the autophagic process. Finally, we uncovered a new survival mechanism in AMPK-deficient neurons--cell cannibalism.
自噬在细胞存活中起着重要作用,它在饥饿时为细胞提供营养物质,或者清除错误折叠的蛋白质和受损的细胞器,从而预防退行性疾病。相反,自噬过程也被认为是一种细胞死亡机制。目前尚不清楚决定自噬在细胞存活中是有益还是有害的情况。我们最近表明,在缺乏功能性 AMPK 酶(AMP 激活的蛋白激酶)并遭受严重代谢应激的神经元中,诱导自噬是有害的。我们进一步证明,自噬和 AMPK 之间存在负反馈回路,相互关联,可防止自噬过程的过度和破坏性刺激。最后,我们在 AMPK 缺陷神经元中发现了一种新的生存机制——细胞自噬。