Bioessays

Curtsinger, Heather D.; Martínez‐Absalón, Sofía; Liu, Yuchang; Lopatkin, Allison J.

doi: 10.1002/bies.202400164pmid: 39529437

Bacterial conjugation, wherein DNA is transferred between cells through direct contact, is highly prevalent in complex microbial communities and is responsible for spreading myriad genes related to human and environmental health. Despite their importance, much remains unknown regarding the mechanisms driving the spread and persistence of these plasmids in situ. Studies have demonstrated that transferring, acquiring, and maintaining a plasmid imposes a significant metabolic burden on the host. Simultaneously, emerging evidence suggests that the presence of a conjugative plasmid can also provide both obvious and unexpected benefits to their host and local community. Combined, this highlights a continuous cost‐benefit tradeoff at the population level, likely contributing to overall plasmid abundance and long‐term persistence. Yet, while the metabolic burdens of plasmid conjugation, and their causes, are widely studied, their attendant potential advantages are less clear. Here, we summarize current perspectives on conjugative plasmids’ metabolic burden and then highlight the lesser‐appreciated yet critical benefits that plasmid‐mediated metabolic burdens may provide. We argue that this largely unexplored tradeoff is critical to both a fundamental theory of microbial populations and engineering applications and therefore warrants further detailed study.

Ohba, Akinobu; Yamaguchi, Hiroshi

doi: 10.1002/bies.202400190pmid: 39600072

Endothermic animals expend significant energy to maintain high body temperatures, which offers adaptability to varying environmental conditions. However, this high metabolic rate requires increased food intake. In conditions of low environmental temperature and scarce food resources, some endothermic animals enter a hypometabolic state known as torpor to conserve energy. Torpor involves a marked reduction in body temperature, heart rate, respiratory rate, and locomotor activity, enabling energy conservation. Despite their biological significance and potential medical applications, the neuronal mechanisms regulating torpor still need to be fully understood. Recent studies have focused on fasting‐induced daily torpor in mice due to their suitability for advanced neuroscientific techniques. In this review, we highlight recent advances that extend our understanding of neuronal mechanisms regulating torpor. We also discuss unresolved issues in this research field and future directions.

Wali, Jibran A.; Ni, Duan; Raubenheimer, David; Simpson, Stephen J.

doi: 10.1002/bies.202400071pmid: 39506509

The global obesity epidemic results from a complex interplay of genetic and environmental factors, with diet being a prominent modifiable element driving weight gain and adiposity. Although excess intake of energetic macronutrients is implicated in causing obesity, ongoing debate centers on whether sugar or fat or both are driving the rising obesity rates. This has led to competing models of obesity such as the “Carbohydrate Insulin Model”, the “Energy Balance Model”, and the “Fructose Survival Hypothesis”. Conflicting evidence from studies designed to focus on individual energetic macronutrients or energy rather than macronutrient mixtures underlies this disagreement. Recent research in humans and animals employing the nutritional geometry framework (NGF) emphasizes the importance of considering interactions among dietary components. Protein interacts with carbohydrates, fats, and dietary energy density to influence both calorie intake (“protein leverage”) and, directly and indirectly, metabolic physiology and adiposity. Consideration of these interactions can help to reconcile different models of obesity, and potentially cast new light on obesity interventions.

Kemna, Koen; Burg, Mirjam; Lankester, Arjan; Giera, Martin

doi: 10.1002/bies.202400154pmid: 39506498

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo‐SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.

Whitlock, Jarred M.; Chernomordik, Leonid V.

doi: 10.1002/bies.202400206pmid: 39506368

As life extended into eukaryota, a great host of strategies emerged in the pursuit of cellular life. Some cells have been successful in solitude, some moved into cooperatives (i.e., multicellular organisms), but one additional strategy emerged. Throughout eukaryotes, many of the diverse multicellular cooperatives took life in partnership one step further. These cells came together and lost their singularity in the expanse of syncytial life. Recently in our search for this elusive “how”, we discovered the intriguing peculiarity of a nuclear, RNA‐binding protein living a second life as a fusion manager at the surface of developing osteoclasts, ushering them into syncytia 1. It is from here that we will develop several thoughts about the advantages of multinucleated cells and discuss how these fusing cells pass through several hallmarks of cell death. We will propose that cell fusion shares much with cell death because cell fusion is a death of sorts for the cells that undergo it – a death of the life that was and the beginning of new life in a community without borders.

Lafont, Elodie; Chevet, Eric

doi: 10.1002/bies.202400230pmid: 39600056

Due to various intracellular and external cues, cellular organelles are frequently stressed in both physiological and pathological conditions. Sensing these stresses initiates various signaling pathways which may lead to adaptation of the stressed cells or trigger its their death. At the unicellular level, this stress signaling involves a crosstalk between different organelles. At the multicellular level, such pathways can contribute to indicate the presence of a stressed cell to its neighboring cells. Here, we highlight the crucial and diverse roles played by Ubiquitin and Ubiquitin‐like modification in organelle stress signaling.

Li, Tiantian; Hogenhout, Saskia A.; Huang, Weijie

doi: 10.1002/bies.202400161pmid: 39600079

Targeted protein degradation (TPD) has emerged as a highly promising approach for eliminating disease‐associated proteins in the field of drug discovery. Among the most advanced TPD technologies, PROteolysis TArgeting Chimera (PROTAC), functions by bringing a protein of interest (POI) into proximity with an E3 ubiquitin ligase, leading to ubiquitin (Ub)‐dependent proteasomal degradation. However, the designs of most PROTACs are based on the utilization of a limited number of available E3 ligases, which significantly restricts their potential. Recent studies have shown that phytoplasmas, a group of bacterial plant pathogens, have developed several E3‐ and ubiquitin‐independent proteasomal degradation (UbInPD) mechanisms for breaking down host targets. This suggests an alternative approach for substrate recruitment and TPD. Here, we present existing evidence that supports the feasibility of UbInPD in eukaryotic cells and propose candidate proteins that can serve as docking sites for the development of E3‐independent PROTACs.

Kivelä, Riikka

doi: 10.1002/bies.202400278pmid: 39651833

Gendrel, Anne‐Valerie

doi: 10.1002/bies.202400256pmid: 39593263

Rashad, Sherif

doi: 10.1002/bies.202400213pmid: 39600051

Transfer RNA (tRNA) modifications play an important role in regulating mRNA translation at the codon level. tRNA modifications can influence codon selection and optimality, thus shifting translation toward specific sets of mRNAs in a dynamic manner. Queuosine (Q) is a tRNA modification occurring at the wobble position. In eukaryotes, queuosine is synthesized by the tRNA‐guanine trans‐glycosylase (TGT) complex, which incorporates the nucleobase queuine (or Qbase) into guanine of the GUN anticodons. Queuine is sourced from gut bacteria and dietary intake. Q was recently shown to be critical for cellular responses to oxidative and mitochondrial stresses, as well as its potential role in neurodegenerative diseases and brain health. These unique features of Q provide an interesting insight into the regulation of mRNA translation by gut bacteria, and the potential health implications. In this review, Q biology is examined in the light of recent literature and nearly 4 decades of research. Q's role in neuropsychiatric diseases and cancer is highlighted and discussed. Given the recent interest in Q, and the new findings, more research is needed to fully comprehend its biological function and disease relevance, especially in neurobiology.