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Regulation of Metabolism by Cell Cycle Regulators

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 15437

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Special Issue Editor

Dr. Escoté Xavier

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Guest Editor

Eurecat, Technology Centre of Catalunya. Nutrition and Health Unit, Reus, Spain
Interests: Brown adipose tissue activation; browning; white adipose tissue metabolism; liver metabolism; NAFLD; precision nutrition; healthy aging; obesity; metabolic syndrome

Special Issue Information

Dear Colleagues,

In mammals, the cell cycle regulatory machinery is composed of about 20 different cyclin-dependent kinases (CDKs), which, together with their partners, cyclins, form complexes that activate or inhibit various substrates by phosphorylation. In addition, there are numerous specific inhibitors and activators of these complexes. The importance of these complexes is evident, because their miss-regulation may lead to some pathophysiological processes such as cancer. However, only one CDK is essential for the proper control of cell cycle progression. Thus, the emerging question is what is the purpose of the other CDKs and cell cycle members? The answer can be found in new physiological functions, in addition to cell cycle regulation, because during evolution, cell cycle proteins acquire new functions that go beyond driving the cell cycle, such as regulating the cell metabolism in certain cell types or specific environmental situations.

The aim of this Special Issue of IJMS is to cover new insights into the mechanisms regulated by the cell cycle machinery beyond cell cycle regulation. Important topics of this Special Issue also involve the role of CDKs, cyclins, and their inhibitors and activators in energy processes, endocrine regulation, inflammation, and metabolism, as well as the possibility of targeting these proteins in therapeutics and clinical applications. Original investigations in preclinical models and/or translational human studies, as well as reviewing manuscripts, are cordially invited for this Special Issue.

Dr. Escoté Xavier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

CDKs
cyclins
metabolism
physiology
endocrine control
energy processes
inflammation
liver
muscle
pancreas
adipose tissues

Published Papers (5 papers)

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Research

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18 pages, 4707 KiB

Open AccessArticle

Thyroid Hormone Receptor α Controls the Hind Limb Metamorphosis by Regulating Cell Proliferation and Wnt Signaling Pathways in Xenopus tropicalis

by Yuta Tanizaki, Yuki Shibata, Hongen Zhang and Yun-Bo Shi

Int. J. Mol. Sci. 2022, 23(3), 1223; https://doi.org/10.3390/ijms23031223 - 22 Jan 2022

Cited by 6 | Viewed by 1726

Abstract

Thyroid hormone (T3) receptors (TRs) mediate T3 effects on vertebrate development. We have studied Xenopus tropicalis metamorphosis as a model for postembryonic human development and demonstrated that TRα knockout induces precocious hind limb development. To reveal the molecular pathways regulated by TRα during limb development, we performed chromatin immunoprecipitation- and RNA-sequencing on the hind limb of premetamorphic wild type and TRα knockout tadpoles, and identified over 700 TR-bound genes upregulated by T3 treatment in wild type but not TRα knockout tadpoles. Interestingly, most of these genes were expressed at higher levels in the hind limb of premetamorphic TRα knockout tadpoles than stage-matched wild-type tadpoles, suggesting their derepression upon TRα knockout. Bioinformatic analyses revealed that these genes were highly enriched with cell cycle and Wingless/Integrated (Wnt) signaling-related genes. Furthermore, cell cycle and Wnt signaling pathways were also highly enriched among genes bound by TR in wild type but not TRα knockout hind limb. These findings suggest that direct binding of TRα to target genes related to cell cycle and Wnt pathways is important for limb development: first preventing precocious hind limb formation by repressing these pathways as unliganded TR before metamorphosis and later promoting hind limb development during metamorphosis by mediating T3 activation of these pathways. Full article

(This article belongs to the Special Issue Regulation of Metabolism by Cell Cycle Regulators)

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19 pages, 4420 KiB

Open AccessArticle

Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress

by Celia Salazar, Miriam Barros, Alvaro A. Elorza and Lina María Ruiz

Int. J. Mol. Sci. 2022, 23(1), 389; https://doi.org/10.3390/ijms23010389 - 30 Dec 2021

Cited by 2 | Viewed by 2433

Abstract

Mitochondrial respiratory supercomplex formation requires HIG2A protein, which also has been associated with cell proliferation and cell survival under hypoxia. HIG2A protein localizes in mitochondria and nucleus. DNA methylation and mRNA expression of the HIGD2A gene show significant alterations in several cancers, suggesting a role for HIG2A in cancer biology. The present work aims to understand the dynamics of the HIG2A subcellular localization under cellular stress. We found that HIG2A protein levels increase under oxidative stress. H₂O₂ shifts HIG2A localization to the mitochondria, while rotenone shifts it to the nucleus. HIG2A protein colocalized at a higher level in the nucleus concerning the mitochondrial network under normoxia and hypoxia (2% O₂). Hypoxia (2% O₂) significantly increases HIG2A nuclear colocalization in C2C12 cells. In HEK293 cells, chemical hypoxia with CoCl₂ (>1% O₂) and FCCP mitochondrial uncoupling, the HIG2A protein decreased its nuclear localization and shifted to the mitochondria. This suggests that the HIG2A distribution pattern between the mitochondria and the nucleus depends on stress and cell type. HIG2A protein expression levels increase under cellular stresses such as hypoxia and oxidative stress. Its dynamic distribution between mitochondria and the nucleus in response to stress factors suggests a new communication system between the mitochondria and the nucleus. Full article

(This article belongs to the Special Issue Regulation of Metabolism by Cell Cycle Regulators)

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17 pages, 9527 KiB

Open AccessArticle

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

by Ignacio Colón-Mesa, Marta Fernández-Galilea, Neira Sáinz, Marta Lopez-Yus, Jose M. Artigas, José Miguel Arbonés-Mainar, Elisa Félix-Soriano, Xavier Escoté and María Jesús Moreno-Aliaga

Int. J. Mol. Sci. 2021, 22(21), 11745; https://doi.org/10.3390/ijms222111745 - 29 Oct 2021

Cited by 4 | Viewed by 2031

Abstract

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis. Full article

(This article belongs to the Special Issue Regulation of Metabolism by Cell Cycle Regulators)

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21 pages, 7717 KiB

Open AccessArticle

The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

by Luisa F. Bustamante-Jaramillo, Celia Ramos and Cristina Martín-Castellanos

Int. J. Mol. Sci. 2021, 22(11), 5483; https://doi.org/10.3390/ijms22115483 - 22 May 2021

Cited by 2 | Viewed by 2546

Abstract

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events. Full article

(This article belongs to the Special Issue Regulation of Metabolism by Cell Cycle Regulators)

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Review

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30 pages, 3535 KiB

Open AccessReview

Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness

by Ada Nowosad and Arnaud Besson

Int. J. Mol. Sci. 2022, 23(4), 2290; https://doi.org/10.3390/ijms23042290 - 18 Feb 2022

Cited by 10 | Viewed by 5791

Abstract

Initially described as lytic bodies due to their degradative and recycling functions, lysosomes play a critical role in metabolic adaptation to nutrient availability. More recently, the contribution of lysosomal proteins to cell signaling has been established, and lysosomes have emerged as signaling hubs that regulate diverse cellular processes, including cell proliferation and cell fate. Deciphering these signaling pathways has revealed an extensive crosstalk between the lysosomal and cell cycle machineries that is only beginning to be understood. Recent studies also indicate that a number of lysosomal proteins are involved in the regulation of embryonic and adult stem cell fate and identity. In this review, we will focus on the role of the lysosome as a signaling platform with an emphasis on its function in integrating nutrient sensing with proliferation and cell cycle progression, as well as in stemness-related features, such as self-renewal and quiescence. Full article

(This article belongs to the Special Issue Regulation of Metabolism by Cell Cycle Regulators)

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