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Zinc at the crossroads of exercise and proteostasis.

ABSTRACT: Zinc is an essential element for all forms of life, and one in every ten human proteins is a zinc protein. Zinc has catalytic, structural and signalling functions and its correct homeostasis affects many cellular processes. Zinc deficiency leads to detrimental consequences, especially in tissues with high demand such as skeletal muscle. Zinc cellular homeostasis is tightly regulated by different transport and buffer protein systems. Specifically, in skeletal muscle, zinc has been found to affect myogenesis and muscle regeneration due to its effects on muscle cell activation, proliferation and differentiation. In relation to skeletal muscle, exercise has been shown to modulate zinc serum and urinary levels and could directly affect cellular zinc transport. The oxidative stress induced by exercise may provide the basis for the mild zinc deficiency observed in athletes and could have severe consequences on health and sport performance. Proteostasis is induced during exercise and zinc plays an essential role in several of the associated pathways.

SUBMITTER: Hernandez-Camacho JD

PROVIDER: S-EPMC7284914 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Zinc at the crossroads of exercise and proteostasis.

Hernández-Camacho Juan Diego JD Vicente-García Cristina C Parsons Douglas S DS Navas-Enamorado Ignacio I

Redox biology 20200401

Zinc is an essential element for all forms of life, and one in every ten human proteins is a zinc protein. Zinc has catalytic, structural and signalling functions and its correct homeostasis affects many cellular processes. Zinc deficiency leads to detrimental consequences, especially in tissues with high demand such as skeletal muscle. Zinc cellular homeostasis is tightly regulated by different transport and buffer protein systems. Specifically, in skeletal muscle, zinc has been found to affect ...[more]

PMID: 32273258

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Project description:The metal-resistant beta-proteobacterium Cupriavidus metallidurans is also able to survive conditions of metal starvation. We show that zinc-starved cells can substitute some of the required zinc with cobalt but not with nickel ions. The zinc importer ZupT was necessary for this process but was not essential for either zinc or cobalt import. The cellular cobalt content was also influenced by the two COG0523-family proteins, CobW2 and CobW3. Pulse-chase experiments with radioactive and isotope-enriched zinc demonstrated that both proteins interacted with ZupT to control the cellular flow-equilibrium of zinc, a central process of zinc homeostasis. Moreover, an antagonistic interplay of CobW2 and CobW3 in the presence of added cobalt caused a growth defect in mutant cells devoid of the cobalt efflux system DmeF. Full cobalt resistance also required a synergistic interaction of ZupT and DmeF. Thus, the two transporters along with CobW2 and CobW3 interact to control cobalt homeostasis in a process that depends on zinc availability. Because ZupT, CobW2, and CobW3 also direct zinc homeostasis, this process links the control of cobalt and zinc homeostasis, which subsequently protects C. metallidurans against cadmium stress and general metal starvation.IMPORTANCEIn bacterial cells, zinc ions need to be allocated to zinc-dependent proteins without disturbance of this process by other transition metal cations. Under zinc-starvation conditions, C. metallidurans floods the cell with cobalt ions, which protect the cell against cadmium toxicity, help withstand metal starvation, and provide cobalt to metal-promiscuous paralogs of essential zinc-dependent proteins. The number of cobalt ions needs to be carefully controlled to avoid a toxic cobalt overload. This is accomplished by an interplay of the zinc importer ZupT with the COG0523-family proteins, CobW3, and CobW2. At high external cobalt concentrations, this trio of proteins additionally interacts with the cobalt efflux system, DmeF, so that these four proteins form an inextricable link between zinc and cobalt homeostasis.

Dataset Information

Zinc at the crossroads of exercise and proteostasis.

Publications

Zinc at the crossroads of exercise and proteostasis.

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