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Sirtuins in Stress Response, Genome Integrity and Cell Physiology
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Sirtuins in Stress Response, Genome Integrity and Cell Physiology

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (18 March 2021) | Viewed by 14084

Special Issue Editors

Dr. Alejandro Vaquero

E-Mail Website
Guest Editor
Josep Carreras Leukaemia Research Institute, Barcelona, Spain
Interests: epigenetics; sirtuins; chromatin; stress response; genome stability; aging
Dr. Lourdes Serrano

E-Mail Website
Guest Editor
BMCC, New York, NY, USA

Special Issue Information

Dear Colleagues,

The members of the family of NAD+-dependent enzymes, also known as Sirtuins, play a key role in the response to a wide range of stress conditions from genotoxic to oxidative and metabolic stress. Sirtuins show a high degree of functional diversification related to two different enzymatic activities (deacylation and ADP-ribosylation), a wide range of substrates, and a highly diverse pattern of cellular and organ distribution. Studies in the last twenty years have involved Sirtuins in the epigenetic regulation of stress-related expression programs, protection of genome stability from DNA damage signaling to regulation of cell cycle, metabolic adaptation, cell fate, and differentiation, among others. Reflecting the importance of their function, Sirtuins have been involved in many human pathologies, including cancer, cardiovascular and neurodegenerative diseases, endocrine-related pathologies, and aging.

This Special Issue aims to provide a current perspective on the important contribution of Sirtuins to the maintenance of cellular and organismal homeostasis. In recent years, the Sirtuin field has experienced several remarkable advances at different levels from basic to translational research, addressing important questions about physiological processes and disease. Among them, it is worth mentioning the characterization of new Sirtuin enzymatic activities, the development of specific Sirtuin modulators, new evidence supporting the role of Sirtuins in chromatin organization and integrity, new metabolic networks, as well as novel functional connections to cancer and aging-related pathologies. Considering the relevance of these discoveries, this issue will be particularly timely in helping to bring focus to the most promising areas of Sirtuin research.

Dr. Alejandro Vaquero
Prof. Lourdes Serrano
Guest Editors

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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • Sirtuins 
  • Stress response 
  • Genome stability 
  • NAD+dependent deacylation 
  • ADP-ribosylation 
  • Chromatin 
  • Metabolic homeostasis 
  • Epigenetics 
  • Aging 
  • Sirtuin modulators

Published Papers (4 papers)

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Research

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14 pages, 2452 KiB  
Article
Mammalian SIRT6 Represses Invasive Cancer Cell Phenotypes through ATP Citrate Lyase (ACLY)-Dependent Histone Acetylation
by Wei Zheng, Luisa Tasselli, Tie-mei Li and Katrin F. Chua
Genes 2021, 12(9), 1460; https://doi.org/10.3390/genes12091460 - 21 Sep 2021
Cited by 7 | Viewed by 2847
Abstract
The modulation of dynamic histone acetylation states is key for organizing chromatin structure and modulating gene expression and is regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. The mammalian SIRT6 protein, a member of the Class III HDAC Sirtuin family of [...] Read more.
The modulation of dynamic histone acetylation states is key for organizing chromatin structure and modulating gene expression and is regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes. The mammalian SIRT6 protein, a member of the Class III HDAC Sirtuin family of NAD+-dependent enzymes, plays pivotal roles in aging, metabolism, and cancer biology. Through its site-specific histone deacetylation activity, SIRT6 promotes chromatin silencing and transcriptional regulation of aging-associated, metabolic, and tumor suppressive gene expression programs. ATP citrate lyase (ACLY) is a nucleo-cytoplasmic enzyme that produces acetyl coenzyme A (acetyl-CoA), which is the required acetyl donor for lysine acetylation by HATs. In addition to playing a central role in generating cytosolic acetyl-CoA for de novo lipogenesis, a growing body of work indicates that ACLY also functions in the nucleus where it contributes to the nutrient-sensitive regulation of nuclear acetyl-CoA availability for histone acetylation in cancer cells. In this study, we have identified a novel function of SIRT6 in controlling nuclear levels of ACLY and ACLY-dependent tumor suppressive gene regulation. The inactivation of SIRT6 in cancer cells leads to the accumulation of nuclear ACLY protein and increases nuclear acetyl-CoA pools, which in turn drive locus-specific histone acetylation and the expression of cancer cell adhesion and migration genes that promote tumor invasiveness. Our findings uncover a novel mechanism of SIRT6 in suppressing invasive cancer cell phenotypes and identify acetyl-CoA responsive cell migration and adhesion genes as downstream targets of SIRT6. Full article
(This article belongs to the Special Issue Sirtuins in Stress Response, Genome Integrity and Cell Physiology)
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Review

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26 pages, 4631 KiB  
Review
Nuclear Sirtuins and the Aging of the Immune System
by Andrés Gámez-García and Berta N. Vazquez
Genes 2021, 12(12), 1856; https://doi.org/10.3390/genes12121856 - 23 Nov 2021
Cited by 12 | Viewed by 4086
Abstract
The immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseases, suggesting [...] Read more.
The immune system undergoes major changes with age that result in altered immune populations, persistent inflammation, and a reduced ability to mount effective immune responses against pathogens and cancer cells. Aging-associated changes in the immune system are connected to other age-related diseases, suggesting that immune system rejuvenation may provide a feasible route to improving overall health in the elderly. The Sir2 family of proteins, also called sirtuins, have been broadly implicated in genome homeostasis, cellular metabolism, and aging. Sirtuins are key responders to cellular and environmental stress and, in the case of the nuclear sirtuins, they do so by directing responses to chromatin that include gene expression regulation, retrotransposon repression, enhanced DNA damage repair, and faithful chromosome segregation. In the immune system, sirtuins instruct cellular differentiation from hematopoietic precursors and promote leukocyte polarization and activation. In hematopoietic stem cells, sirtuins safeguard quiescence and stemness to prevent cellular exhaustion. Regulation of cytokine production, which, in many cases, requires NF-κB regulation, is the best-characterized mechanism by which sirtuins control innate immune reactivity. In adaptive immunity, sirtuins promote T cell subset differentiation by controlling master regulators, thereby ensuring an optimal balance of helper (Th) T cell-dependent responses. Sirtuins are very important for immune regulation, but the means by which they regulate immunosenescence are not well understood. This review provides an integrative overview of the changes associated with immune system aging and its potential relationship with the roles of nuclear sirtuins in immune cells and overall organismal aging. Given the anti-aging properties of sirtuins, understanding how they contribute to immune responses is of vital importance and may help us develop novel strategies to improve immune performance in the aging organism. Full article
(This article belongs to the Special Issue Sirtuins in Stress Response, Genome Integrity and Cell Physiology)
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19 pages, 812 KiB  
Review
Sirtuins as Metabolic Regulators of Immune Cells Phenotype and Function
by Lídia Fortuny and Carlos Sebastián
Genes 2021, 12(11), 1698; https://doi.org/10.3390/genes12111698 - 26 Oct 2021
Cited by 11 | Viewed by 3076
Abstract
Beyond its role on the conversion of nutrients into energy and biomass, cellular metabolism is actively involved in the control of many physiological processes. Among these, it is becoming increasingly evident that specific metabolic pathways are associated with the phenotype of several immune [...] Read more.
Beyond its role on the conversion of nutrients into energy and biomass, cellular metabolism is actively involved in the control of many physiological processes. Among these, it is becoming increasingly evident that specific metabolic pathways are associated with the phenotype of several immune cell types and, importantly, are crucial in controlling their differentiation, proliferation, and effector functions, thus shaping the immune response against pathogens and tumors. In this context, data generated over the last decade have uncovered mammalian sirtuins as important regulators of cellular metabolism, immune cell function, and cancer. Here, we summarize our current knowledge on the roles of this family of protein deacylases on the metabolic control of immune cells and their implications on immune-related diseases and cancer. Full article
(This article belongs to the Special Issue Sirtuins in Stress Response, Genome Integrity and Cell Physiology)
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13 pages, 1720 KiB  
Review
SIRT7 Acts as a Guardian of Cellular Integrity by Controlling Nucleolar and Extra-Nucleolar Functions
by Poonam Kumari, Shahriar Tarighi, Thomas Braun and Alessandro Ianni
Genes 2021, 12(9), 1361; https://doi.org/10.3390/genes12091361 - 30 Aug 2021
Cited by 11 | Viewed by 3263
Abstract
Sirtuins are key players for maintaining cellular homeostasis and are often deregulated in different human diseases. SIRT7 is the only member of mammalian sirtuins that principally resides in the nucleolus, a nuclear compartment involved in ribosomal biogenesis, senescence, and cellular stress responses. The [...] Read more.
Sirtuins are key players for maintaining cellular homeostasis and are often deregulated in different human diseases. SIRT7 is the only member of mammalian sirtuins that principally resides in the nucleolus, a nuclear compartment involved in ribosomal biogenesis, senescence, and cellular stress responses. The ablation of SIRT7 induces global genomic instability, premature ageing, metabolic dysfunctions, and reduced stress tolerance, highlighting its critical role in counteracting ageing-associated processes. In this review, we describe the molecular mechanisms employed by SIRT7 to ensure cellular and organismal integrity with particular emphasis on SIRT7-dependent regulation of nucleolar functions. Full article
(This article belongs to the Special Issue Sirtuins in Stress Response, Genome Integrity and Cell Physiology)
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