Seminars in cell & developmental biology最新文献

Mitochondria are complex organelles with an outer membrane enveloping a second inner membrane that creates a vast matrix space partitioned by pockets or cristae that join the peripheral inner membrane with several thin junctions. Several micrometres long, mitochondria are generally close to 300 nm in diameter, with membrane layers separated by a few tens of nanometres. Ultrastructural data from electron microscopy revealed the structure of these mitochondria, while conventional optical microscopy revealed their extraordinary dynamics through fusion, fission, and migration processes but its limited resolution power restricted the possibility to go further. By overcoming the limits of light diffraction, Super-Resolution Microscopy (SRM) now offers the potential to establish the links between the ultrastructure and remodelling of mitochondrial membranes, leading to major advances in our understanding of mitochondria’s structure-function. Here we review the contributions of SRM imaging to our understanding of the relationship between mitochondrial structure and function. What are the hopes for these new imaging approaches which are particularly important for mitochondrial pathologies?

The evolutionary forces underlying the rapid evolution in sequences and functions of new genes remain a mystery. Adaptation by natural selection explains the evolution of some new genes. However, many new genes perform sex-biased functions that have rapidly evolved over short evolutionary time scales, suggesting that new gene evolution may often be driven by conflicting selective pressures on males and females. It is well established that such sexual conflict (SC) plays a central role in maintaining phenotypic and genetic variation within populations, but the role of SC in driving new gene evolution remains essentially unknown. This review explores the connections between SC and new gene evolution through discussions of the concept of SC, the phenotypic and genetic signatures of SC in evolving populations, and the molecular mechanisms by which SC could drive the evolution of new genes. We synthesize recent work in this area with a discussion of the case of Apollo and Artemis, two extremely young genes (<200,000 years) in Drosophila melanogaster, which offered the first empirical insights into the evolutionary process by which SC could drive the evolution of new genes. These new duplicate genes exhibit the hallmarks of sexually antagonistic selection: rapid DNA and protein sequence evolution, essential sex-specific functions in gametogenesis, and complementary sex-biased expression patterns. Importantly, Apollo is essential for male fitness but detrimental to female fitness, while Artemis is essential for female fitness but detrimental to male fitness. These sexually antagonistic fitness effects and complementary changes to expression, sequence, and function suggest that these duplicates were selected for mitigating SC, but that SC has not been fully resolved. Finally, we propose Sexual Conflict Drive as a self-driven model to interpret the rapid evolution of new genes, explain the potential for SC and sexually antagonistic selection to contribute to long-term evolution, and suggest its utility for understanding the rapid evolution of new genes in gametogenesis.

Stress granules and P-bodies are conserved cytoplasmic biomolecular condensates whose assembly and composition are well documented, but whose clearance mechanisms remain controversial or poorly described. Such understanding could provide new insight into how cells regulate biomolecular condensate formation and function, and identify therapeutic strategies in disease states where aberrant persistence of stress granules in particular is implicated. Here, I review and compare the contributions of chaperones, the cytoskeleton, post-translational modifications, RNA helicases, granulophagy and the proteasome to stress granule and P-body clearance. Additionally, I highlight the potentially vital role of RNA regulation, cellular energy, and changes in the interaction networks of stress granules and P-bodies as means of eliciting clearance. Finally, I discuss evidence for interplay of distinct clearance mechanisms, suggest future experimental directions, and suggest a simple working model of stress granule clearance.

The ribosomal DNA locus (rDNA) is central for the functioning of cells because it encodes ribosomal RNAs, key components of ribosomes, and also because of its links to fundamental metabolic processes, with significant impact on genome integrity and aging. The repetitive nature of the rDNA gene units forces the locus to maintain sequence homogeneity through recombination processes that are closely related to genomic stability. The co-presence of basic DNA transactions, such as replication, transcription by major RNA polymerases, and recombination, in a defined and restricted area of the genome is of particular relevance as it affects the stability of the rDNA locus by both direct and indirect mechanisms. This condition is well exemplified by the rDNA of Saccharomyces cerevisiae. In this review we summarize essential knowledge on how the complexity and overlap of different processes contribute to the control of rDNA and genomic stability in this model organism.

TERRA is a class of telomeric repeat-containing RNAs that are expressed from telomeres in multiple organisms. TERRA transcripts play key roles in telomere maintenance and their physiological levels are essential to maintain the integrity of telomeric DNA. Indeed, deregulated TERRA expression or its altered localization can impact telomere stability by multiple mechanisms including fueling transcription-replication conflicts, promoting resection of chromosome ends, altering the telomeric chromatin, and supporting homologous recombination. Therefore, a fine-tuned control of TERRA is important to maintain the integrity of the genome. Several studies have reported that different cell lines express substantially different levels of TERRA. Most importantly, TERRA levels markedly vary among telomeres of a given cell type, indicating the existence of telomere-specific regulatory mechanisms which may help coordinate TERRA functions. TERRA molecules contain distinct subtelomeric sequences, depending on their telomere of origin, which may instruct specific post-transcriptional modifications or mediate distinct functions. In addition, all TERRA transcripts share a repetitive G-rich sequence at their 3′ end which can form DNA:RNA hybrids and fold into G-quadruplex structures. Both structures are involved in TERRA functions and can critically affect telomere stability. In this review, we examine the mechanisms controlling TERRA levels and the impact of their telomere-specific regulation on telomere stability. We compare evidence obtained in different model organisms, discussing recent advances as well as controversies in the field. Furthermore, we discuss the importance of DNA:RNA hybrids and G-quadruplex structures in the context of TERRA biology and telomere maintenance.

Mitochondria play diverse and essential roles in eukaryotic cells, and plants are no exception. Plant mitochondria have several differences from their metazoan and fungal cousins: they often exist in a fragmented state, move rapidly on actin rather than microtubules, have many plant-specific metabolic features and roles, and usually contain only a subset of the complete mtDNA genome, which itself undergoes frequent recombination. This arrangement means that exchange and complementation is essential for plant mitochondria, and recent work has begun to reveal how their collective dynamics and resultant “social networks” of encounters support this exchange, connecting plant mitochondria in time rather than in space. This review will argue that this social network perspective can be extended to a “societal network”, where mitochondrial dynamics are an essential part of the interacting cellular society of organelles and biomolecules. Evidence is emerging that mitochondrial dynamics allow optimal resolutions to competing cellular priorities; we will survey this evidence and review potential future research directions, highlighting that plant mitochondria can help reveal and test principles that apply across other kingdoms of life. In parallel with this fundamental cell biology, we also highlight the translational “One Health” importance of plant mitochondrial behaviour – which is exploited in the production of a vast amount of crops consumed worldwide – and the potential for multi-objective optimisation to understand and rationally re-engineer the evolved resolutions to these tensions.

Apoptosis is the best described form of regulated cell death, and was, until relatively recently, considered irreversible once particular biochemical points-of-no-return were activated. In this manuscript, we examine the mechanisms cells use to escape from a self-amplifying death signaling module. We discuss the role of feedback, dynamics, propagation, and noise in apoptotic signaling. We conclude with a revised model for the role of apoptosis in animal development, homeostasis, and disease.

The successful treatment of oncological malignancies which results in long-term disease control or the complete eradication of cancerous cells necessitates the onset of adaptive immune responses targeting tumor-specific antigens. Such desirable anticancer immunity can be triggered via the induction of immunogenic cell death (ICD) of cancer cells, thus converting malignant cells into an in situ vaccine that elicits T cell mediated adaptive immune responses and establishes durable immunological memory. The exploration of ICD for cancer treatment has been subject to extensive research. However, functional heterogeneity among ICD activating therapies in many cases requires specific co-medications to achieve full-blown efficacy. Here, we described the hallmarks of ICD and classify ICD activators into three distinct functional categories namely, according to their mode of action: (i) ICD inducers, which increase the immunogenicity of malignant cells, (ii) ICD sensitizers, which prime cellular circuitries for ICD induction by conventional cytotoxic agents, and (iii) ICD enhancers, which improve the perception of ICD signals by antigen presenting dendritic cells. Altogether, ICD induction, sensitization and enhancement offer the possibility to convert well-established conventional anticancer therapies into immunotherapeutic approaches that activate T cell-mediated anticancer immunity.