20E (20-Hydroxyecdysone) is a central steroid hormone that orchestrates developmental changes and metamorphosis in arthropods. While its molecular mechanisms have been recognized for some time, detailed elucidation has primarily emerged in the past decade. PCD (Programmed cell death), including apoptosis, necrosis, efferocytosis, pyroptosis, ferroptosis, and autophagy, plays a crucial role in regulated cell elimination, which is vital for cells’ development and tissue homeostasis. This review summarizes recent findings on 20E signaling regulated autophagy and apoptosis in insects, including Drosophila melanogaster, Bombyx mori, Helicoverpa armigera, and other species. Firstly, we comprehensively explore the biosynthesis of the sterol hormone 20E and its subsequent signal transduction in various species. Then, we focus on the involvement of 20E in regulating autophagy and apoptosis, elucidating its roles in both developmental contexts and bacterial infection scenarios. Furthermore, our discussion unfolds as a panoramic exposition, where we delve into the fundamental questions with our findings, anchoring them within the grander scheme of our study in insects. Deepening the understanding of 20E-autophagy/apoptosis axis not only underscores the intricate tapestry of endocrine networks, but also offers fresh perspectives on the adaptive mechanisms that have evolved in the face of environmental challenges.
Autophagy, a crucial cellular mechanism responsible for degradation and recycling of intracellular components, is modulated by an intricate network of molecular signals. Its paradoxical involvement in oncogenesis, acting as both a tumor suppressor and promoter, has been underscored in recent studies. Central to this regulatory network are the epigenetic modifications of DNA and RNA methylation, notably the presence of N6-methyldeoxyadenosine (6mA) in genomic DNA and N6-methyladenosine (m6A) in eukaryotic mRNA. The 6mA modification in genomic DNA adds an extra dimension of epigenetic regulation, potentially impacting the transcriptional dynamics of genes linked to autophagy and, especially, cancer. Conversely, m6A modification, governed by methyltransferases and demethylases, influences mRNA stability, processing, and translation, affecting genes central to autophagic pathways. As we delve deeper into the complexities of autophagy regulation, the importance of these methylation modifications grows more evident. The interplay of 6mA, m6A, and autophagy points to a layered regulatory mechanism, illuminating cellular reactions to a range of conditions. This review delves into the nexus between DNA 6mA and RNA m6A methylation and their influence on autophagy in cancer contexts. By closely examining these epigenetic markers, we underscore their promise as therapeutic avenues, suggesting novel approaches for cancer intervention through autophagy modulation.
The bio-prospecting of bioactive phytochemicals from invasive flora presents a sustainable paradigm for the ecologically conscious management of major invasive pest S. invicta. Ageratina adenophora, while recognized for its allelopathic insecticidal properties, exhibits poorly characterized toxicological profiles and mechanistic underpinnings against S. invicta, warranting systematic investigation to elucidate its mode of action. This study elucidates the bioactive insecticidal compounds of A. adenophora and their toxicological impacts on S. invicta, including behavioral, metabolic, and enzymatic perturbations, via liquid chromatography–mass spectrometry (LC-MS) profiling. The ethanol extracts of the roots, stems, and leaves of A. adenophora have shown control effects on S. invicta, with an LC50 (50% lethal concentration) of 331.847, 188.256, and 166.253 mg/mL at 48 h, respectively. Metabolite profiling of A. adenophora revealed that safranal and dihydrocoumarin are relatively high in plant leaves, and they showed significant insecticidal activity and behavioral inhibitory effects on S. invicta with LC50 349.042 mg/L and 118.336 mg/L at 48 h, respectively. Notably, these two bioactive compounds disrupted the normal energy production through glucose metabolism and the citrate cycle, which eventually led to the death of S. invicta. Further, these two compounds also activated the detoxification metabolic pathway of S. invicta. These findings provide a theoretical basis for the use of these bioactive compounds in the integrated management of S. invicta and may lead to the development of a new biopesticide.
Tip60, a key histone acetyltransferase of the MYST family and member of the nuclear multimeric protein complex (NuA4), regulates the activity and stability of proteins involved in the cell cycle, DNA damage responses, autophagy, etc. However, the function and regulatory mechanism of Tip60 homolog in Bombyx mori are not elucidated. In the present study, Bombyx Tip60 (BmTip60) was functionally identified. Developmental profiles showed that the protein levels and nuclear localization of BmTip60 peaked in fat body during the larval–pupal metamorphosis when autophagy was intensive; simultaneously, the BmTip60 protein migrated to form an upper band as detected by Western blot. Interestingly, the upper band of BmTip60 was reduced by λ-phosphatase treatment, indicating that it was a phosphorylated form of BmTip60. Results showed that BmTip60 was promoted by starvation but not 20-hydroxyecdysone treatment. Transcription factor AMP-activated protein kinase (AMPK) affected by starvation was pivotal for BmTip60 protein migration. In addition, one mammalian phosphorylation site was identified in BmTip60 at Ser99, the constitutive-activation mutation of Ser99 to Asp99 but not its inactive mutation to Ala99 significantly upregulated autophagy, showing the critical role of phosphorylation at Ser99 for BmTip60-mediated autophagy. In conclusion, the starvation-AMPK axis promotes BmTip60 in B. mori, which was requisite for autophagy induction. These results reveal a regulatory mechanism of histone acetyltransferase Tip60 homologs by phosphorylation in insects, and sheds light on further related studies of acetylation regulation.
RNA methylation, characterized by modifications such as N6-methyladenosine, 5-methylcytosine, and N1-methyladenosine plays a crucial role in post-transcriptional gene regulation across diverse biological systems. While research on RNA methylation has predominantly focused on mammals, particularly its roles in epigenetic regulation and cancer biology, recent studies in insects have begun to explore their extensive functions in insect physiology. This review examines the mechanisms by which RNA methylation regulates growth, development, reproduction, environmental adaptation, and immune response in insects, providing insights into the biological characteristics of these organisms without prematurely speculating on pest control strategies. It aims to offer valuable insights into the role of RNA methylation in insect biology and resistance.