Mitochondrial sirtuin 3 and various cell death modalities

Yapryntseva, Maria A.; Maximchik, Polina V.; Zhivotovsky, Boris; Gogvadze, Vladimir

doi:10.3389/fcell.2022.947357

Cited by 9 publications

(4 citation statements)

References 131 publications

(115 reference statements)

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“…SIRT3 is the only sirtuin affecting human lifespan, playing a key role in several mitochondrial metabolic processes such as oxidative stress and energy metabolism [150] (Figure 6). Several studies highlighted the involvement of SIRT3 in neurodegenerative disorders [151], ischemic stroke, traumatic brain injury, intracerebral hemorrhage, neuro-inflammation along with heart failure, oxidative stress, autophagy, and apoptosis [152][153][154]. The beneficial effects of Citrus flavonoids on human health have been deeply investigated, representing important ingredients for nutraceuticals and functional foods [155].…”

Section: Sirt3mentioning

confidence: 99%

“…Under hyperglycemic conditions, HSP, the aglycone form of HES present in peels of Citrus fruits, was shown to exert protective effects by counteracting LPS-induced secretion of pro-inflammatory cytokines in THP-1 macrophages. The mechanism underlying this anti-inflammatory Several studies highlighted the involvement of SIRT3 in neurodegenerative disorders [151], ischemic stroke, traumatic brain injury, intracerebral hemorrhage, neuroinflammation along with heart failure, oxidative stress, autophagy, and apoptosis [152][153][154]. The beneficial effects of Citrus flavonoids on human health have been deeply investigated, representing important ingredients for nutraceuticals and functional foods [155].…”

Section: Sirt3mentioning

confidence: 99%

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Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

Lombardo,

Russo,

Maugeri

et al. 2024

IJMS

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Sirtuins (SIRTs) belong to the family of nicotine adenine dinucleotide (NAD+)-dependent class III histone deacetylases, which come into play in the regulation of epigenetic processes through the deacetylation of histones and other substrates. The human genome encodes for seven homologs (SIRT1-7), which are localized into the nucleus, cytoplasm, and mitochondria, with different enzymatic activities and regulatory mechanisms. Indeed, SIRTs are involved in different physio-pathological processes responsible for the onset of several human illnesses, such as cardiovascular and neurodegenerative diseases, obesity and diabetes, age-related disorders, and cancer. Nowadays, it is well-known that Citrus fruits, typical of the Mediterranean diet, are an important source of bioactive compounds, such as polyphenols. Among these, flavonoids are recognized as potential agents endowed with a wide range of beneficial properties, including antioxidant, anti-inflammatory, hypolipidemic, and antitumoral ones. On these bases, we offer a comprehensive overview on biological effects exerted by Citrus flavonoids via targeting SIRTs, which acted as modulator of several signaling pathways. According to the reported studies, Citrus flavonoids appear to be promising SIRT modulators in many different pathologies, a role which might be potentially evaluated in future therapies, along with encouraging the study of those SIRT members which still lack proper evidence on their support.

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Section: Sirt3mentioning

confidence: 99%

Section: Sirt3mentioning

confidence: 99%

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

Lombardo,

Russo,

Maugeri

et al. 2024

IJMS

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“…While the direct free radical scavenging actions of melatonin and its metabolites are generally considered to be receptor-independent, its actions on the redox-related enzymes require the intervention of receptors ( Figure 1 ). The deacetylation and activation of mitochondrial superoxide dismutase (SOD2) also requires the stimulation of sirtuin 3 (SIRT3), a major multifunctional NAD+-dependent histone deacetylating enzyme located in mitochondrial matrix [ 68 ]. Upregulation of SIRT3 in mitochondria has been functionally linked to delayed cellular aging including that of the oocyte [ 69 ].…”

Section: Melatonin: Redox Mechanisms For Preserving Reproductive Healthmentioning

confidence: 99%

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

et al. 2023

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Aging has a major detrimental effect on the optimal function of the ovary with changes in this organ preceding the age-related deterioration in other tissues, with the middle-aged shutdown leading to infertility. Reduced fertility and consequent inability to conceive by women in present-day societies who choose to have children later in life leads to increased frustration. Melatonin is known to have anti-aging properties related to its antioxidant and anti-inflammatory actions. Its higher follicular fluid levels relative to blood concentrations and its likely synthesis in the oocyte, granulosa, and luteal cells suggest that it is optimally positioned to interfere with age-associated deterioration of the ovary. Additionally, the end of the female reproductive span coincides with a significant reduction in endogenous melatonin levels. Thus, the aims are to review the literature indicating melatonin production in mitochondria of oocytes, granulosa cells, and luteal cells, identify the multiple processes underlying changes in the ovary, especially late in the cessation of the reproductive life span, summarize the physiological and molecular actions of melatonin in the maintenance of normal ovaries and in the aging ovaries, and integrate the acquired information into an explanation for considering melatonin in the treatment of age-related infertility. Use of supplemental melatonin may help preserve fertility later in life and alleviate frustration in women delaying childbearing age, reduce the necessity of in vitro fertilization–embryo transfer (IVF-ET) procedures, and help solve the progressively increasing problem of non-aging-related infertility in women throughout their reproductive life span. While additional research is needed to fully understand the effects of melatonin supplementation on potentially enhancing fertility, studies published to date suggest it may be a promising option for those struggling with infertility.

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“…Mitochondria are not only the center of cellular energy metabolism but also a crucial organelle in regulating cell death [10,11]. The role of SIRT3 in cardiac protection has been gradually revealed, inhibiting programmed cell death of myocardial cells by regulating antioxidant defense and energy metabolism within the mitochondria [12,13]. SIRT3 can alleviate oxidative stress by activating antioxidant enzymes [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Novel Mechanism of SIRT3 Regulation in Cardiac Inflammatory Injury: The Key Role of MITOL

Li,

Wang

2024

HSF

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Background: Myocardial injury is a common heart disease that involves various forms of cell death, including pyroptosis. Lipopolysaccharide (LPS) can simulate the inflammatory response of cardiomyocytes, resulting in their damage. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, has been shown to play a role in cardiac protection. This study aimed to investigate whether SIRT3 mitigates inflammation-induced cardiomyocyte pyroptosis and alleviates LPS-induced myocardial injury via the mitochondrial ubiquitin ligase (MITOL)-dependent mechanism. Methods: Mouse and H9C2 cardiomyocyte models were used to simulate myocardial inflammatory injury by LPS treatment. Cardiac ultrasound, protein expression analysis, mRNA expression detection, and serum biochemical indicators were used to assess the extent of myocardial injury. The EdU experiment was conducted to detect cell proliferation capacity. DCFH-DA fluorescence was used to measure Reactive Oxygen Species (ROS) levels. JC-1 probe analysis was used to assess the aggregate/monomer ratio in different treatment groups. Furthermore, SIRT3 treatment and MITOL silencing experiments were conducted to explore the impact of SIRT3 on cardiomyocyte pyroptosis and whether it functions through MITOL. Scanning electron microscopy experiments were conducted to assess the reversal of the protective effect of SIRT3 by silencing MITOL. Results: The experimental results showed that LPS treatment significantly impaired mouse cardiac function, increased the expression of pyroptosis-related proteins in cardiomyocytes, elevated serum myocardial injury indicators, and increased the mRNA expression of inflammatory factors (tumor necrosis factor-alpha (TNFα) and interleukin-1β (IL-1β)). SIRT3 treatment significantly reduced LPS-induced myocardial injury, improved cardiac function, reduced the expression of pyroptosis-related proteins, and decreased inflammatory factors. Silencing MITOL reversed the protective effect of SIRT3 on cardiomyocyte injury, suggesting that SIRT3 exerted its therapeutic effect through MITOL. Conclusion: This study revealed that SIRT3 mitigated inflammation-induced cardiomyocyte pyroptosis via a MITOL-dependent mechanism, thereby alleviating LPS-induced myocardial injury. This finding provides a new molecular target for the treatment of myocardial inflammation-related diseases and lays a theoretical foundation for the development of cardiac protection strategies. Future research can further explore the potential application of the SIRT3-MITOL axis in cardiac diseases, providing effective treatment methods for cardiac patients.

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Mitochondrial sirtuin 3 and various cell death modalities

Cited by 9 publications

References 131 publications

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue

Novel Mechanism of SIRT3 Regulation in Cardiac Inflammatory Injury: The Key Role of MITOL

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