Lee C Y, Baehrecke E H
Center for Agricultural Biotechnology, University of Maryland Biotechnology Institute, College Park, Maryland 20742, USA.
Development. 2001 Apr;128(8):1443-55. doi: 10.1242/dev.128.8.1443.
Apoptosis and autophagy are morphologically distinct forms of programmed cell death. While autophagy occurs during the development of diverse organisms and has been implicated in tumorigenesis, little is known about the molecular mechanisms that regulate this type of cell death. Here we show that steroid-activated programmed cell death of Drosophila salivary glands occurs by autophagy. Expression of p35 prevents DNA fragmentation and partially inhibits changes in the cytosol and plasma membranes of dying salivary glands, suggesting that caspases are involved in autophagy. The steroid-regulated BR-C, E74A and E93 genes are required for salivary gland cell death. BR-C and E74A mutant salivary glands exhibit vacuole and plasma membrane breakdown, but E93 mutant salivary glands fail to exhibit these changes, indicating that E93 regulates early autophagic events. Expression of E93 in embryos is sufficient to induce cell death with many characteristics of apoptosis, but requires the H99 genetic interval that contains the rpr, hid and grim proapoptotic genes to induce nuclear changes diagnostic of apoptosis. In contrast, E93 expression is sufficient to induce the removal of cells by phagocytes in the absence of the H99 genes. These studies indicate that apoptosis and autophagy utilize some common regulatory mechanisms.
凋亡和自噬是程序性细胞死亡在形态学上不同的形式。虽然自噬发生在多种生物体的发育过程中，并与肿瘤发生有关，但对于调节这种细胞死亡类型的分子机制知之甚少。在这里，我们表明果蝇唾液腺的类固醇激活程序性细胞死亡是通过自噬发生的。p35的表达可防止DNA片段化，并部分抑制垂死唾液腺的细胞质和质膜变化，表明半胱天冬酶参与自噬。唾液腺细胞死亡需要类固醇调节的BR-C、E74A和E93基因。BR-C和E74A突变的唾液腺表现出液泡和质膜破裂，但E93突变的唾液腺未表现出这些变化，表明E93调节早期自噬事件。E93在胚胎中的表达足以诱导具有许多凋亡特征的细胞死亡，但需要包含rpr、hid和grim促凋亡基因的H99遗传区间来诱导诊断凋亡的核变化。相比之下，在没有H99基因的情况下，E93的表达足以诱导吞噬细胞清除细胞。这些研究表明，凋亡和自噬利用一些共同的调节机制。
