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Biomolecules,
2023]
Heme is an iron-containing tetrapyrrole that plays a critical role in various biological processes, including oxygen transport, electron transport, signal transduction, and catalysis. However, free heme is hydrophobic and potentially toxic to cells. Organisms have evolved specific pathways to safely transport this essential but toxic macrocycle within and between cells. The bacterivorous soil-dwelling nematode <i>Caenorhabditis elegans</i> is a powerful animal model for studying heme-trafficking pathways, as it lacks the ability to synthesize heme but instead relies on specialized trafficking pathways to acquire, distribute, and utilize heme. Over the past 15 years, studies on this microscopic animal have led to the identification of a number of heme-trafficking proteins, with corresponding functional homologs in vertebrates. In this review, we provide a comprehensive overview of the heme-trafficking proteins identified in <i>C. elegans</i> and their corresponding homologs in related organisms.
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Curr Opin Hematol,
2012]
PURPOSE OF REVIEW: Heme biosynthesis requires a series of enzymatic reactions that take place in the cytosol and the mitochondria as well as the proper intercellular and intracellular trafficking of iron. Heme can also be acquired by intestinal absorption and intercellular transport. The purpose of this review is to highlight recent work on heme and iron transport with an emphasis on their relevance in erythropoiesis. RECENT FINDINGS: Whereas the enzymes responsible for heme biosynthesis have been identified, transport mechanisms for iron, heme, or heme synthesis intermediates are only emerging. Recent studies have shed light on how these molecules are transported among various cellular compartments, as well as tissues. Much of this progress can be attributed to the use of model organisms such as S. cerevisiae, C. elegans, D. rerio, and M. musculus. Genetic studies in these models have led to the identification of several new genes involved in heme metabolism. Although our understanding has greatly improved, it is highly likely that other regulators exist and additional work is required to characterize the pathways by which heme and iron are transported within the erythron. SUMMARY: The identification of heme and iron transport mechanisms will improve our understanding of blood development and provide new insight into human blood disorders.
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Mol Cell Neurosci,
2018]
Axon regeneration is a fundamental and conserved process that allows the nervous system to repair circuits after trauma. Due to its conserved genome, transparent body, and relatively simple neuroanatomy, C. elegans has become a powerful model organism for studying the cellular and molecular mechanisms underlying axon regeneration. Various studies from different model organisms have found microtubule dynamics to be pivotal to axon regrowth. In this review, we will discuss the latest findings on how microtubule dynamics are regulated during axon regeneration in C. elegans. Understanding the mechanisms of axon regeneration will aid in the development of more effective therapeutic strategies for treatments of diseases involving disconnection of axons, such as spinal cord injury and stroke.
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Antioxid Redox Signal,
2015]
SIGNIFICANCE: The nematode Caenorhabditis elegans is a widely used model organism for research into aging. However, nematodes diverged from other animals between 600 and 1300 million years ago. Beyond the intuitive impression that some aspects of aging appear to be universal, is there evidence that insights into the aging process of nematodes may be applicable to humans? RECENT ADVANCES: There have been a number of results in nematodes that appear to contradict long-held beliefs about mechanisms and causes of aging. For example, ablation of several key antioxidant systems has often failed to result in lifespan shortening in C. elegans. CRITICAL ISSUES: While it is clear that some central signaling pathways controlling lifespan are broadly conserved across large evolutionary distances, it is less clear to what extent downstream molecular mechanisms of aging are conserved. In this review we discuss the biology of C. elegans and mammals in the context of aging and age-dependent diseases. We consider evidence from studies that attempt to investigate basic, possibly conserved mechanisms of aging especially in the context of the free radical theory of aging. Practical points, such as the need for blinding of lifespan studies and for appropriate biomarkers, are also considered. FUTURE DIRECTIONS: As data on the aging process(es) in different organisms increase, it is becoming increasingly clear that there are both conserved (public) and private aspects to aging. It is important to explore the dividing lines between these two aspects and to be aware of the large gray areas in-between.
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Chem Cent J,
2015]
Age-associated neurodegenerative disorders such as Alzheimer's disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential.
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Biotechnol Adv,
2013]
Olfaction in Caenorhabditis elegans is a versatile and sensitive strategy to seek food and avoid danger by sensing volatile chemicals emitted by the targets. The ability to sense attractive odor is mainly accomplished by the AWA and AWC neurons. Previous studies have shown the components of the olfaction signal pathway in these two amphid chemosensory neurons, but integration of the individual signaling components requires further elucidation. Here we review the progresses in our understanding of signal pathways for attractive olfaction involving AWA and AWC neurons, and discuss how the different signal molecules might employ the common molecular cascades to transduce the olfactory system and guide behavior in each neuron.
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Trends Cell Biol,
2011]
Understanding the mechanisms of axon regeneration is of great importance to the development of therapeutic treatments for spinal cord injury or stroke. Axon regeneration has long been studied in diverse vertebrate and invertebrate models, but until recently had not been analyzed in the genetically tractable model organism Caenorhabditis elegans. The small size, simple neuroanatomy, and transparency of C. elegans allows single fluorescently labeled axons to be severed in live animals using laser microsurgery. Many neurons in C. elegans are capable of regenerative regrowth, and can in some cases re-establish functional connections. Large-scale genetic screens have begun to elucidate the genetic basis of axon regrowth.
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Cheng B, Huang Y, Chen H, Chen C, Zhang J, Zeng L, Li H, Li Y, Shi C, Xiang M, Peng Y, Wang C
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Environ Pollut,
2022]
Environmental pollutants such as heavy metals, nano/microparticles, and organic compounds have been detected in a wide range of environmental media, causing long-term exposure in various organisms and even humans through breathing, contacting, ingestion, and other routes. Long-term exposure to environmental pollutants in organisms or humans promotes exposure of offspring to parental and environmental pollutants, and subsequently results in multiple biological defects in the offspring. This review dialectically summarizes and discusses the existing studies using Caenorhabditis elegans (C. elegans) as a model organism to explore the multi/transgenerational toxicity and potential underlying molecular mechanisms induced by environmental pollutants following parental or successive exposure patterns. Parental and successive exposure to environmental pollutants induces various biological defects in C. elegans across multiple generations, including multi/transgenerational developmental toxicity, neurotoxicity, reproductive toxicity, and metabolic disturbances, which may be transmitted to progeny through reactive oxygen species-induced damage, epigenetic mechanisms, insulin/insulin-like growth factor-1 signaling pathway. This review aims to arouse researchers' interest in the multi/transgenerational toxicity of pollutants and hopes to explore the possible long-term effects of environmental pollutants on organisms and even humans, as well as to provide constructive suggestions for the safety and management of emerging alternatives.
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J Cell Biochem,
2013]
microRNA (miRNA) is a family of small, non-coding RNA first discovered as an important regulator of development in Caenorhabditis elegans (C. elegans). Numerous miRNAs have been found in C. elegans, and some of them are well conserved in many organisms. Though, the biologic function of miRNAs in C. elegans was largely unknown, more and more studies support the idea that miRNA is an important molecular for C. elegans. In this review, we revisit the research progress of miRNAs in C. elegans related with development, aging, cancer, and neurodegenerative diseases and compared the function of miRNAs between C. elegans and human.
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Methods Mol Biol,
2006]
The genome of the nematode Caenorhabditis elegans was the first animal genome sequenced. Subsequent sequencing of the Caenorhabditis briggsae genome enabled a comparison of the genomes of two nematode species. In this chapter, we describe the methods that we used to compare the C. elegans genome to that of C. briggsae. We discuss how these methods could be developed to compare the C. elegans and C. briggsae genomes to those of Caenorhabditis remanei, C. n. sp. represented by strains PB2801 and CB5161, among others (1), and Caenorhabditis japonica, which are currently being sequenced.