Context-Dependent Roles for SIRT2 and SIRT3 in Tumor Development Upon Calorie Restriction or High Fat Diet

Ahmed, Mohamed A.; O’Callaghan, Carol; Chang, Elliot D; Jiang, Haiyan; Vassilopoulos, Athanassios

doi:10.3389/fonc.2019.01462

Cited by 12 publications

(3 citation statements)

References 47 publications

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“…In short, SIRT3 promotes oxidative phosphorylation and inhibits glycolysis in the overall regulation of mitochondrial metabolism 80 , 81 . Intriguingly, a recent study found that SIRT3 changes to an oncogene to promote HFD-induced tumorigenesis in mice 82 . Therefore, the role of SIRT3 in cancer appears context-dependent 83 .…”

Section: Sirt3 and Human Diseasementioning

confidence: 99%

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Zhang¹,

Xiang²,

Liu³

et al. 2020

Theranostics

232

182

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Sirtuin 3 (SIRT3) is one of the most prominent deacetylases that can regulate acetylation levels in mitochondria, which are essential for eukaryotic life and inextricably linked to the metabolism of multiple organs. Hitherto, SIRT3 has been substantiated to be involved in almost all aspects of mitochondrial metabolism and homeostasis, protecting mitochondria from a variety of damage. Accumulating evidence has recently documented that SIRT3 is associated with many types of human diseases, including age-related diseases, cancer, heart disease and metabolic diseases, indicating that SIRT3 can be a potential therapeutic target. Here we focus on summarizing the intricate mechanisms of SIRT3 in human diseases, and recent notable advances in the field of small-molecule activators or inhibitors targeting SIRT3 as well as their potential therapeutic applications for future drug discovery.

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Section: Sirt3 and Human Diseasementioning

confidence: 99%

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Zhang¹,

Xiang²,

Liu³

et al. 2020

Theranostics

232

182

View full text Add to dashboard Cite

show abstract

“…A similar case was observed with acetylation of p53. Ahmed et al investigated the cross-link between p53 and SIRT3 in mice on a normal diet and a high-fat diet and their effect on survival and carcinogenesis [ 162 ]. The authors found that p53 expression significantly increased the lifespan of mice on a high-fat diet and decreased carcinogenesis, while SIRT3 expression attenuated its effect.…”

Section: Other Atp-dependent Feedback Mechanisms To Stop Overactivate...mentioning

confidence: 99%

A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

Zhelev

Aoki

Lazarova

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cancer metabolism is an extensively studied field since the discovery of the Warburg effect about 100 years ago and continues to be increasingly intriguing and enigmatic so far. It has become clear that glycolysis is not the only abnormally activated metabolic pathway in the cancer cells, but the same is true for the fatty acid synthesis (FAS) and mevalonate pathway. In the last decade, a lot of data have been accumulated on the pronounced mitochondrial fatty acid oxidation (mFAO) in many types of cancer cells. In this article, we discuss how mFAO can escape normal regulation under certain conditions and be overactivated. Such abnormal activation of mitochondrial β-oxidation can also be combined with mutations in certain enzymes of the Krebs cycle that are common in cancer. If overactivated β-oxidation is combined with other common cancer conditions, such as dysfunctions in the electron transport complexes, and/or hypoxia, this may alter the redox state of the mitochondrial matrix. We propose the idea that the altered mitochondrial redox state and/or inhibited Krebs cycle at certain segments may link mitochondrial β-oxidation to the citrate-malate shuttle instead to the Krebs cycle. We call this abnormal metabolic condition “β-oxidation shuttle”. It is unconventional mFAO, a separate metabolic pathway, unexplored so far as a source of energy, as well as a source of cataplerosis, leading to biomass accumulation, accelerated oxygen consumption, and ultimately a source of proliferation. It is inefficient as an energy source and must consume significantly more oxygen per mole of ATP produced when combined with acetyl-CoA consuming pathways, such as the FAS and mevalonate pathway.

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“…Similarly, SIRT3 enhances the activity of GDH to promote the TCA cycle, thereby increasing the occurrence of lymphoma ( 66 ). Intriguingly, inhibition of SIRT3 expression may reduce the carcinogenic effect induced by high-fat diets (HFDs), suggesting that SIRT3 is served as an oncogene ( 76 ).…”

Section: Regulation Of Cancer Metabolism Reprogramming By Sirt3mentioning

confidence: 99%

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

Zhao

Zhou

et al. 2022

Front. Oncol.

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Sirtuin 3 (SIRT3), the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, acts as a metabolic modulator mainly located in mitochondria via regulating the process of the relevant biochemical processes by targeting crucial mediators. Recently, owing to its dual role in cancer, SIRT3 has attracted extensive attention. Cancer cells have different metabolic patterns from normal cells, and SIRT3-mediated metabolism reprogramming could be critical in the cancer context, which is closely related to the mechanism of metabolism reprogramming, metastasis, and chemoresistance in tumor cells. Therefore, it is crucial to elucidate the relevant pathological mechanisms and take appropriate countermeasures for the progression of clinical strategies to inhibit the development of cancer. In this review, existing available data on the regulation of cancer metabolism reprogramming, metastasis, and chemoresistance progression of SIRT3 are detailed, as well as the status quo of SIRT3 small molecule modulators is updated in the application of cancer therapy, aiming to highlight strategies directly targeting SIRT3-mediated tumor-suppressing and tumor-promoting, and provide new approaches for therapy application. Furthermore, we offer an effective evidence-based basis for the evolvement of potential personalized therapy management strategies for SIRT3 in cancer settings.

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Context-Dependent Roles for SIRT2 and SIRT3 in Tumor Development Upon Calorie Restriction or High Fat Diet

Cited by 12 publications

References 47 publications

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance

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