Details

Autor(en) / Beteiligte

• Poels, J
• Spasić, M R
• Gistelinck, M
• Mutert, J
• Schellens, A
• Callaerts, P
• Norga, K K

Titel

Autophagy and phagocytosis-like cell cannibalism exert opposing effects on cellular survival during metabolic stress

Ist Teil von

• Cell death and differentiation, 2012-10, Vol.19 (10), p.1590-1601

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2012

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.