Advances in characterization of SIRT3 deacetylation targets in mitochondrial function

Wang, Shuhan; Zhang, Junli; Deng, Xiaoling; Zhao, Yong; Xu, Ke

doi:10.1016/j.biochi.2020.08.021

Cited by 31 publications

(24 citation statements)

References 131 publications

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“…Apart from calcium overload and toxic reactive oxygen species (ROS), impaired mitochondrial energy production has been implicated in heart and brain injuries following successful resuscitation (8)(9)(10). Mitochondrial Sirtuin3, which belongs to an evolutionary conserved family of nicotinamide adenine dinucleotide (NAD + )-dependent deacetylases (Sirtuins), is a key regulator of the mitochondrial respiratory chain and adenosine triphosphate (ATP) production (11,12). It has been reported that activation of Sirtuin3 protected the heart and brain against ischemia and reperfusion injury (13,14).…”

mentioning

confidence: 99%

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest

Xiao

Zhang

et al. 2021

Critical Care Medicine

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To investigate the therapeutic potential and underlying mechanisms of exogenous nicotinamide adenine dinucleotide + on postresuscitation myocardial and neurologic dysfunction in a rat model of cardiac arrest.DESIGN: Thirty-eight rats were randomized into three groups: 1) Sham, 2) Control, and 3) NAD. Except for the sham group, untreated ventricular fibrillation for 6 minutes followed by cardiopulmonary resuscitation was performed in the control and NAD groups. Nicotinamide adenine dinucleotide + (20 mg/kg) was IV administered at the onset of return of spontaneous circulation. SETTING:University-affiliated research laboratory. SUBJECTS:Sprague-Dawley rats. INTERVENTIONS:Nicotinamide adenine dinucleotide + . MEASUREMENTS AND MAIN RESULTS:Hemodynamic and myocardial function were measured at baseline and within 4 hours following return of spontaneous circulation. Survival analysis and Neurologic Deficit Score were performed up to 72 hours after return of spontaneous circulation. Adenosine triphosphate (adenosine triphosphate) level was measured in both brain and heart tissue. Mitochondrial respiratory chain function, acetylation level, and expression of Sirtuin3 and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 (NDUFA9) in isolated mitochondrial protein from both brain and heart tissue were evaluated at 4 hours following return of spontaneous circulation. The results demonstrated that nicotinamide adenine dinucleotide + treatment improved mean arterial pressure (at 1 hr following return of spontaneous circulation, 94.69 ± 4.25 mm Hg vs 89.57 ± 7.71 mm Hg; p < 0.05), ejection fraction (at 1 hr following return of spontaneous circulation, 62.67% ± 6.71% vs 52.96% ± 9.37%; p < 0.05), Neurologic Deficit Score (at 24 hr following return of spontaneous circulation, 449.50 ± 82.58 vs 339.50 ± 90.66; p < 0.05), and survival rate compared with that of the control group. The adenosine triphosphate level and complex I respiratory were significantly restored in the NAD group compared with those of the control group. In addition, nicotinamide adenine dinucleotide + treatment activated the Sirtuin3 pathway, down-regulating acetylated-NDUFA9 in the isolated mitochondria protein. CONCLUSIONS:Exogenous nicotinamide adenine dinucleotide + treatment attenuated postresuscitation myocardial and neurologic dysfunction. The responsible mechanisms may involve the preservation of mitochondrial complex I respiratory capacity and adenosine triphosphate production, which involves the Sirtuin3-NDUFA9 deacetylation.

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confidence: 99%

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest

Xiao

Zhang

et al. 2021

Critical Care Medicine

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“…SIRT3 is mainly located in the mitochondria and functions as a vital role in regulating the glucose metabolism, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) detoxification, electron transport chain (ETC), fatty acid (FA) metabolism, mitochondrial unfolded protein response (UPR mt ), autophagy, etc. (23)(24)(25). SIRT3 could directly deacetylate pyruvate dehydrogenase (PDH) and glutamate oxaloacetate transaminase 2 (GOT2) to regulate glucose metabolism (26).…”

Section: Sirt3 Deacetylationmentioning

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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“…As one of the most basic characteristics of life, energy metabolism mainly includes the release, transfer, storage, and utilization of energy. SIRT3 could promote energy production by deacetylating the subunit proteins of the mitochondrial respiratory chain complex ( 27 ). For instance, SIRT3 could maintain intracellular metabolic balance by deacetylating ATP synthase beta ( 28 , 29 ).…”

Section: The Physiological Function Of Sirt3mentioning

confidence: 99%

The Role of SIRT3 in the Osteoporosis

Wang

2022

Front. Endocrinol.

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SIRT3 is an NAD+-dependent deacetylase in the mitochondria with an extensive ability to regulate mitochondrial morphology and function. It has been reported that SIRT3 participates in the occurrence and development of many aging-related diseases. Osteoporosis is a common aging-related disease characterized by decreased bone mass and fragility fractures, which has caused a huge burden on society. Current research shows that SIRT3 is involved in the physiological processes of senescence of bone marrow mesenchymal stem cells (BMSCs), differentiation of BMSCs and osteoclasts. However, the specific effects and mechanisms of SIRT3 in osteoporosis are not clear. In the current review, we elaborated on the physiological functions of SIRT3, the cell types involved in bone remodeling, and the role of SIRT3 in osteoporosis. Furthermore, it also provided a theoretical basis for SIRT3 as a therapeutic target for osteoporosis.

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Advances in characterization of SIRT3 deacetylation targets in mitochondrial function

Cited by 31 publications

References 131 publications

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest

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

The Role of SIRT3 in the Osteoporosis

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