Francesca Oppedisano, Salvatore Nesci, Anna Spagnoletta
{"title":"线粒体 sirtuin 3 和天然化合物的作用:翻译后修饰对细胞代谢的影响。","authors":"Francesca Oppedisano, Salvatore Nesci, Anna Spagnoletta","doi":"10.1080/10409238.2024.2377094","DOIUrl":null,"url":null,"abstract":"<p><p>Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD<sup>+</sup>-dependent histone deacetylases and ADP-ribosyltransferases. NAD<sup>+</sup>-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD<sup>+</sup> binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys<sub>280</sub>. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondrial sirtuin 3 and role of natural compounds: the effect of post-translational modifications on cellular metabolism.\",\"authors\":\"Francesca Oppedisano, Salvatore Nesci, Anna Spagnoletta\",\"doi\":\"10.1080/10409238.2024.2377094\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD<sup>+</sup>-dependent histone deacetylases and ADP-ribosyltransferases. NAD<sup>+</sup>-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD<sup>+</sup> binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys<sub>280</sub>. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.</p>\",\"PeriodicalId\":10794,\"journal\":{\"name\":\"Critical Reviews in Biochemistry and Molecular Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Biochemistry and Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/10409238.2024.2377094\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/10409238.2024.2377094","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/11 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Mitochondrial sirtuin 3 and role of natural compounds: the effect of post-translational modifications on cellular metabolism.
Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD+-dependent histone deacetylases and ADP-ribosyltransferases. NAD+-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD+ binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys280. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.
期刊介绍:
As the discipline of biochemistry and molecular biology have greatly advanced in the last quarter century, significant contributions have been made towards the advancement of general medicine, genetics, immunology, developmental biology, and biophysics. Investigators in a wide range of disciplines increasingly require an appreciation of the significance of current biochemical and molecular biology advances while, members of the biochemical and molecular biology community itself seek concise information on advances in areas remote from their own specialties.
Critical Reviews in Biochemistry and Molecular Biology believes that well-written review articles prove an effective device for the integration and meaningful comprehension of vast, often contradictory, literature. Review articles also provide an opportunity for creative scholarship by synthesizing known facts, fruitful hypotheses, and new concepts. Accordingly, Critical Reviews in Biochemistry and Molecular Biology publishes high-quality reviews that organize, evaluate, and present the current status of high-impact, current issues in the area of biochemistry and molecular biology.
Topics are selected on the advice of an advisory board of outstanding scientists, who also suggest authors of special competence. The topics chosen are sufficiently broad to interest a wide audience of readers, yet focused enough to be within the competence of a single author. Authors are chosen based on their activity in the field and their proven ability to produce a well-written publication.