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首页> 外文期刊>Cell death and differentiation >Autophagy and phagocytosis-like cell cannibalism exert opposing effects on cellular survival during metabolic stress
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Autophagy and phagocytosis-like cell cannibalism exert opposing effects on cellular survival during metabolic stress

机译：自噬和吞噬作用样细胞食人性在代谢应激期间对细胞存活产生相反的影响

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Understanding mechanisms controlling neuronal cell death and survival under conditions of altered energy supply (e.g., during stroke) is fundamentally important for the development of therapeutic strategies. The function of autophagy herein is unclear, as both its beneficial and detrimental roles have been described. We previously demonstrated that loss of AMP-activated protein kinase (AMPK), an evolutionarily conserved enzyme that maintains cellular energy balance, leads to activity-dependent degeneration in neuronal tissue. Here, we show that energy depletion in Drosophila AMPK mutants results in increased autophagy that convincingly promotes, rather than rescues, neurodegeneration. The generated excessive autophagic response is accompanied by increased TOR and S6K activity in the absence of an AMPK-mediated negative regulatory feedback loop. Moreover, energy-depleted neurons use a phagocytic-like process as a means to cellular survival at the expense of surrounding cells. Consequently, phagocytosis stimulation by expression of the scavenger receptor Croquemort significantly delays neurodegeneration. This study thus reveals a potentially novel strategy for cellular survival during conditions of extreme energy depletion, resembling xeno-cannibalistic events seen in metastatic tumors. We provide new insights into the roles of autophagy and phagocytosis in the neuronal metabolic stress response and open new avenues into understanding of human disease and development of therapeutic strategies.
机译：理解在能量供应改变的条件下（例如中风期间）控制神经元细胞死亡和存活的机制对于开发治疗策略至关重要。自噬的功能尚不清楚，因为已经描述了它的有益作用和有害作用。我们以前证明了AMP活化蛋白激酶（AMPK）的丢失，这是一种进化上保守的酶，可维持细胞能量平衡，并导致神经元组织中的活动依赖性变性。在这里，我们显示了果蝇AMPK突变体中的能量消耗导致自噬增加，这令人信服地促进而不是挽救神经变性。在没有AMPK介导的负调节反馈回路的情况下，产生的过度自噬反应伴随着TOR和S6K活性的增加。此外，能量消耗不足的神经元使用吞噬样过程作为细胞存活的手段，但以周围细胞为代价。因此，通过清道夫受体Croquemort的表达刺激吞噬作用显着延迟了神经变性。因此，这项研究揭示了在极端能量消耗的情况下细胞存活的潜在新策略，类似于在转移性肿瘤中发现的异食性相食性事件。我们提供有关自噬和吞噬作用在神经元代谢应激反应中的作用的新见解，并为了解人类疾病和开发治疗策略开辟了新途径。

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