Lysosome-related Organelles as Mediators of Metal Homeostasis Original paper
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Metals
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
What was reviewed?
This review focuses on the role of lysosome-related organelles (LROs) in regulating metal homeostasis within cells. It examines various intracellular compartments, including vacuoles, acidocalcisomes, and other lysosome-like structures, and their involvement in metal storage, sequestration, and mobilization. The review provides an in-depth look at how these organelles manage essential metal ions such as copper, zinc, iron, and manganese, ensuring they are available for biochemical processes while also protecting cells from metal toxicity. The paper highlights the specific metal transporters found within these organelles and their role in maintaining a balance between metal availability and cellular needs, especially in response to stress conditions like metal excess or deficiency.
Who was reviewed?
The review does not focus on individual study participants but rather on the biological systems and organelles within cells that are involved in metal homeostasis. Specifically, it covers various model organisms, including yeast (Saccharomyces cerevisiae), plants (Arabidopsis thaliana), algae (Chlamydomonas reinhardtii), and other eukaryotic organisms, as well as the role of specific transporters within these cells. The review discusses the functional characterization of metal transporters and their contributions to metal homeostasis in different cellular compartments such as vacuoles, acidocalcisomes, and the endomembrane system.
What were the most important findings?
The most important findings of the review emphasize the critical role of lysosome-related organelles, such as vacuoles and acidocalcisomes, in the storage and regulation of metal ions within cells. These organelles contain metal transporters that help maintain metal balance by sequestering metals like copper, zinc, and iron. For example, the vacuole in yeast and plants is essential for metal storage and detoxification, with transporters like the NRAMP and CDF families playing significant roles in metal uptake and efflux. The review also highlights the importance of maintaining the acidic environment within these organelles, which is facilitated by V-type ATPases, as a prerequisite for the proper function of these transporters. In plants, the vacuole functions not only in metal storage but also in the regulation of metal distribution, particularly in response to metal deficiency or excess. Furthermore, the review introduces the concept of acidocalcisomes, which are involved in the sequestration of divalent metal ions such as zinc and iron. These organelles are increasingly recognized for their role in metal homeostasis and stress responses.
What are the greatest implications of this review?
The implications of this review are far-reaching in terms of understanding the fundamental mechanisms of metal homeostasis in cells and their potential applications in fields like agriculture, biotechnology, and medicine. A deeper understanding of how lysosome-related organelles manage metal ions can lead to better strategies for mitigating metal toxicity in plants and animals. For example, knowledge about metal storage and transport could inform efforts to engineer crops with improved tolerance to metal contamination, such as cadmium or arsenic in polluted soils. Additionally, the review’s findings could help in developing therapeutic interventions for conditions related to metal imbalances, such as hemochromatosis (iron overload) or Wilson’s disease (copper overload). By focusing on intracellular metal management, the review provides a clearer picture of how cells maintain metal homeostasis, which could lead to novel treatments for diseases caused by disruptions in metal trafficking.
Copper serves as both a vital nutrient and a potential toxin, with its regulation having profound effects on microbial pathogenesis and immune responses. In the body, copper interacts with pathogens, either supporting essential enzyme functions or hindering microbial growth through its toxicity. The gastrointestinal tract, immune cells, and bloodstream are key sites where copper plays a crucial role in controlling infection and maintaining microbial balance. Understanding copper’s interactions with the microbiome and host defenses allows for targeted clinical strategies.
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.