Autophagy-dependent cell death Denton, Donna; Kumar, Sharad
Cell death and differentiation,
03/2019, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Autophagy-dependent cell death can be defined as cell demise that has a strict requirement of autophagy. Although autophagy often accompanies cell death following many toxic insults, the requirement ...of autophagic machinery for cell death execution, as established through specific genetic or chemical inhibition of the process, is highly contextual. During animal development, perhaps the best validated model of autophagy-dependent cell death is the degradation of the larval midgut during larval-pupal metamorphosis, where a number of key autophagy genes are required for the removal of the tissues. Surprisingly though, even in the midgut, not all of the 'canonical' autophagic machinery appears to be required. In other organisms and cancer cells many variations of autophagy-dependent cell death are apparent, pointing to the lack of a unifying cell death pathway. It is thus possible that components of the autophagy machinery are selectively utilised or repurposed for this type of cell death. In this review, we discuss examples of cell death that utilise autophagy machinery (or part thereof), the current knowledge of the complexity of autophagy-dependent cellular demise and the potential mechanisms and regulatory pathways involved in such cell death.
All immature animals undergo remarkable morphological and physiological changes to become mature adults. In winged insects, metamorphic changes either are limited to a few tissues (hemimetaboly) or ...involve a complete reorganization of most tissues and organs (holometaboly). Despite the differences, the genetic switch between immature and adult forms in both types of insects relies on the disappearance of the antimetamorphic juvenile hormone (JH) and the transcription factors Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) during the last juvenile instar. Here, we show that the transcription factor E93 is the key determinant that promotes adult metamorphosis in both hemimetabolous and holometabolous insects, thus acting as the universal adult specifier. In the hemimetabolous insect Blattella germanica , BgE93 is highly expressed in metamorphic tissues, and RNA interference (RNAi)-mediated knockdown of BgE93 in the nymphal stage prevented the nymphal–adult transition, inducing endless reiteration of nymphal development, even in the absence of JH. We also find that BgE93 down-regulated BgKr-h1 and BgBR-C expression during the last nymphal instar of B. germanica , a key step necessary for proper adult differentiation. This essential role of E93 is conserved in holometabolous insects as TcE93 RNAi in Tribolium castaneum prevented pupal–adult transition and produced a supernumerary second pupa. In this beetle, TcE93 also represses expression of TcKr-h1 and TcBR-C during the pupal stage. Similar results were obtained in the more derived holometabolous insect Drosophila melanogaster , suggesting that winged insects use the same regulatory mechanism to promote adult metamorphosis. This study provides an important insight into the understanding of the molecular basis of adult metamorphosis.
In the several years since we last proposed in-depth analysis and guidance for health and nutrition communicators, in light of the evolving information environment, much has changed—mostly for the ...worse, for the more problematic. The communication landscape has become more challenging, public trust in health institutions seems to have experienced further shrinkage, and some of the old rules for disseminating consensus scientific information may need updating. In this article, we analyze recent events/conditions in the ongoing metamorphosis of the communication environment in the cyber age. Included are some observations from a 2022 National Academies of Sciences, Engineering, and Medicine workshop on best practices for nutrition communication, analysis of misinformation concerns, the effect of social media on information delivery, and some updated guidance for communicators.
Highlights ► The JH–Methoprene-tolerant (Met)–cofactor complex regulates specific genes. ► JH regulates larval molting through Krüppel homolog. ► JH regulates metamorphosis by controlling ...ecdysone-induced Broad (Br) expression. ► JH stimulates Tribolium vitellogenesis indirectly via production of specific ILPs. ► Timing of Drosophila optic lobe development and female receptivity requires JH-Met.
A cell-by-cell view of a worm's metamorphosis Pennisi, Elizabeth
Science (American Association for the Advancement of Science),
01/2023, Letnik:
379, Številka:
6629
Journal Article
Recenzirano
Single-cell analysis reveals shifts in identity as shapeless larva becomes wriggling adult.
The Krüppel homolog 1 gene (Kr-h1) has been proposed to play a key role in the repression of insect metamorphosis. Kr-h1 is assumed to be induced by juvenile hormone (JH) via a JH receptor, ...methoprene-tolerant (Met), but the mechanism of induction is unclear. To elucidate the molecular mechanism of Kr-h1 induction, we first cloned cDNAs encoding Kr-h1 (BmKr-h1) and Met (BmMet1 and BmMet2) homologs from Bombyx mori . In a B. mori cell line, BmKr-h1 was rapidly induced by subnanomolar levels of natural JHs. Reporter assays identified a JH response element (k JHRE), comprising 141 nucleotides, located ∼2 kb upstream from the BmKr-h1 transcription start site. The core region of k JHRE (GGCCTCCACGTG) contains a canonical E-box sequence to which Met, a basic helix–loop–helix Per-ARNT-Sim (bHLH–PAS) transcription factor, is likely to bind. In mammalian HEK293 cells, which lack an intrinsic JH receptor, ectopic expression of BmMet2 fused with Gal4DBD induced JH-dependent activity of an upstream activation sequence reporter. Meanwhile, the k JHRE reporter was activated JH-dependently in HEK293 cells only when cotransfected with BmMet2 and BmSRC, another bHLH–PAS family member, suggesting that BmMet2 and BmSRC jointly interact with k JHRE. We also found that the interaction between BmMet2 and BmSRC is dependent on JH. Therefore, we propose the following hypothesis for the mechanism of JH-mediated induction of BmKr-h1 : BmMet2 accepts JH as a ligand, JH-liganded BmMet2 interacts with BmSRC, and the JH/BmMet2/BmSRC complex activates BmKr-h1 by interacting with k JHRE.
PDF
![Unliganded TR[alpha]: A "Sa...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0013-7227/small "Unliganded TR[alpha]: A \"Safety Lock\" to Metamorphosis")
