Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection
Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD<sup>+</sup>-dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activ...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/6/852 |
| _version_ | 1797612832673497088 |
|---|---|
| author | Emanuele Fabbrizi Francesco Fiorentino Vincenzo Carafa Lucia Altucci Antonello Mai Dante Rotili |
| author_facet | Emanuele Fabbrizi Francesco Fiorentino Vincenzo Carafa Lucia Altucci Antonello Mai Dante Rotili |
| author_sort | Emanuele Fabbrizi |
| collection | DOAJ |
| description | Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD<sup>+</sup>-dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activity of proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty acid oxidation, electron transport chain, generation of ketone bodies, nitrogenous waste management, and reactive oxygen species (ROS) detoxification. SIRT5 controls a wide range of aspects of myocardial energy metabolism and plays critical roles in heart physiology and stress responses. Moreover, SIRT5 has a protective function in the context of neurodegenerative diseases, while it acts as a context-dependent tumor promoter or suppressor. In addition, current research has demonstrated that SIRT5 is implicated in the SARS-CoV-2 infection, although opposing conclusions have been drawn in different studies. Here, we review the current knowledge on SIRT5 molecular actions under both healthy and diseased settings, as well as its functional effects on metabolic targets. Finally, we revise the potential of SIRT5 as a therapeutic target and provide an overview of the currently reported SIRT5 modulators, which include both activators and inhibitors. |
| first_indexed | 2024-03-11T06:47:33Z |
| format | Article |
| id | doaj.art-50d237c0de7c477d870476e923f4176a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:47:33Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-50d237c0de7c477d870476e923f4176a2023-11-17T10:12:47ZengMDPI AGCells2073-44092023-03-0112685210.3390/cells12060852Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 InfectionEmanuele Fabbrizi0Francesco Fiorentino1Vincenzo Carafa2Lucia Altucci3Antonello Mai4Dante Rotili5Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Precision Medicine, Università degli Studi della Campania “L. Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, Università degli Studi della Campania “L. Vanvitelli”, 80138 Naples, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Rome, ItalySirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD<sup>+</sup>-dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activity of proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty acid oxidation, electron transport chain, generation of ketone bodies, nitrogenous waste management, and reactive oxygen species (ROS) detoxification. SIRT5 controls a wide range of aspects of myocardial energy metabolism and plays critical roles in heart physiology and stress responses. Moreover, SIRT5 has a protective function in the context of neurodegenerative diseases, while it acts as a context-dependent tumor promoter or suppressor. In addition, current research has demonstrated that SIRT5 is implicated in the SARS-CoV-2 infection, although opposing conclusions have been drawn in different studies. Here, we review the current knowledge on SIRT5 molecular actions under both healthy and diseased settings, as well as its functional effects on metabolic targets. Finally, we revise the potential of SIRT5 as a therapeutic target and provide an overview of the currently reported SIRT5 modulators, which include both activators and inhibitors.https://www.mdpi.com/2073-4409/12/6/852SIRT5sirtuinsHDACsprotein lysine desuccinylationepigeneticSIRT5 modulators |
| spellingShingle | Emanuele Fabbrizi Francesco Fiorentino Vincenzo Carafa Lucia Altucci Antonello Mai Dante Rotili Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection Cells SIRT5 sirtuins HDACs protein lysine desuccinylation epigenetic SIRT5 modulators |
| title | Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection |
| title_full | Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection |
| title_fullStr | Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection |
| title_full_unstemmed | Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection |
| title_short | Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection |
| title_sort | emerging roles of sirt5 in metabolism cancer and sars cov 2 infection |
| topic | SIRT5 sirtuins HDACs protein lysine desuccinylation epigenetic SIRT5 modulators |
| url | https://www.mdpi.com/2073-4409/12/6/852 |
| work_keys_str_mv | AT emanuelefabbrizi emergingrolesofsirt5inmetabolismcancerandsarscov2infection AT francescofiorentino emergingrolesofsirt5inmetabolismcancerandsarscov2infection AT vincenzocarafa emergingrolesofsirt5inmetabolismcancerandsarscov2infection AT luciaaltucci emergingrolesofsirt5inmetabolismcancerandsarscov2infection AT antonellomai emergingrolesofsirt5inmetabolismcancerandsarscov2infection AT danterotili emergingrolesofsirt5inmetabolismcancerandsarscov2infection |