Larval midgut destruction in Drosophila: Not dependent on caspases but suppressed by the loss of autophagy

Department of Haematology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
Autophagy (Impact Factor: 11.75). 01/2010; 6(1):163-5. DOI: 10.4161/auto.6.1.10601
Source: PubMed

ABSTRACT While most programmed cell death (PCD) in animal development is reliant upon the caspase-dependent apoptotic pathway and subsequent cleavage of caspase substrates, we found that PCD in Drosophila larval midgut occurs normally in the absence of the main components of the apoptotic machinery. However, when some of the components of the autophagic machinery were disrupted, midgut destruction was severely delayed. These studies demonstrate that Drosophila midgut PCD is executed by a novel mechanism where caspases are apparently dispensable, but that requires autophagy.

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Available from: Donna Denton, Mar 12, 2014
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    • "However, the developmental programmed cell death in the midgut of D. melanogaster exhibits a different balancing between apoptosis and autophagy. Caspase activity is clearly detectable during the midgut development, but the contribution of caspases to midgut cell death seems limited because their inhibition has no effect on the midgut rearrangement (Denton et al., 2009, 2010). On this basis, the salivary gland and the midgut developmental modifications present a significant difference where the caspase activity and the role of autophagy is concerned. "
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    ABSTRACT: Caspases are frequently considered synonymous with apoptotic cell death. Increasing evidence demonstrates that these proteases may exert their activities in non-apoptotic functions. The non-apoptotic roles of caspases may include developmentally regulated autophagy during insect metamorphosis, as well as neuroblast self-renewal and the immune response. Here, we summarize the established knowledge and the recent advances in the multiple roles of insect caspases to highlight their relevance for physiological processes and survival. Copyright © 2015. Published by Elsevier Ltd.
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    • "Thus, only experimental studies where specific, genetic disruption of autophagy pathway has been shown to delay cell death, are regarded as more compelling evidence for autophagic cell death (Shen et al., 2012). This so far, has only been demonstrated under some special circumstances in mammalian cells (Turcotte et al., 2008; Puissant et al., 2010; Voss et al., 2010) and in Drosophila (Denton et al., 2010). "
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    • "exceptional cases, such as Drosophila development [11]. Accumulating evidence is challenging the concept of autophagic cell death in mammalian cells [12] [13] [14]. "
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    ABSTRACT: Cancer cells have developed novel mechanisms for evading chemotherapy-induced apoptosis and autophagy-associated cell death pathways. Upon the discovery that chemotherapeutics could target these cell death pathways in a manner that was not mutually exclusive, new discoveries about the interrelationship between these two pathways are emerging. Key proteins originally thought to be "autophagy-related proteins" are now found to be involved in either inducing or inhibiting apoptosis. Similarly, apoptosis inhibiting proteins can also block autophagy-associated cell death. One example is the complex formed by the autophagy protein, Beclin 1, and anti-apoptotic protein Bcl-2, which leads to inhibition of autophagy-associated cell death. Researchers have been investigating additional mechanisms that form/disrupt this complex in order to better design chemotherapeutics. This review will highlight the role Bcl-2 and Beclin 1 play in cancer development and drug resistance, as well as the role the Bcl-2:Beclin 1 complex in the switch between autophagy and apoptosis.
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