Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Zhang, Jin; Xiang, Hua; Liu, Jie; Chen, Yi; He, Rong‐Rong; Liu, Bo

doi:10.7150/thno.45922

Cited by 289 publications

(263 citation statements)

References 200 publications

(237 reference statements)

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“…Increased acetylation of the ETC complexes correlates with a reduction in catalytic activity, impaired mitochondrial oxidative phosphorylation and consequently compromised contractile function of the heart. Therefore, approaches that upregulate and/or maintain SIRT3 expression and activity may represent a promising therapeutic strategy to treat or prevent cardiac dysfunction in the setting of MI [ 41 , 43 , 44 ]. In agreement with these reports, the current study demonstrated that the preserved SIRT3 activity in both sEH null mice or t AUCB pre-treated females subjected to MI correlates with enhanced cardiac contractile function compared to WT counterparts.…”

Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Jamieson

Darwesh

Sosnowski

et al. 2021

IJMS

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Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk for MI in females increases as they enter the peri-menopausal period, generally occurring in middle-age. Cytochrome (CYP) 450 metabolizes N-3 and N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. The objective of this study was to characterize oxylipid metabolism in the left ventricle (LV) following ischemic injury in females. Human LV specimens were procured from female patients with ischemic cardiomyopathy (ICM) or non-failing controls (NFC). Female C57BL6 (WT) and sEH null mice averaging 13–16 months old underwent permanent occlusion of the left anterior descending coronary artery (LAD) to induce myocardial infarction. WT (wild type) mice received vehicle or sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB), in their drinking water ad libitum for 28 days. Cardiac function was assessed using echocardiography and electrocardiogram. Protein expression was determined using immunoblotting, mitochondrial activity by spectrophotometry, and cardiac fibre respiration was measured using a Clark-type electrode. A full metabolite profile was determined by LC–MS/MS. sEH was significantly elevated in ischemic LV specimens from patients, associated with fundamental changes in oxylipid metabolite formation and significant decreases in mitochondrial enzymatic function. In mice, pre-treatment with tAUCB or genetic deletion of sEH significantly improved survival, preserved cardiac function, and maintained mitochondrial quality following MI in female mice. These data indicate that sEH may be a relevant pharmacologic target for women with MI. Although future studies are needed to determine the mechanisms, in this pilot study we suggest targeting sEH may be an effective strategy for reducing ischemic injury and mortality in middle-aged females.

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Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Jamieson

Darwesh

Sosnowski

et al. 2021

IJMS

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“…CypD regulates the opening of mitochondrial permeability transition pore by phosphorylating serine residue S191 [ 25 ]. Indeed, SIRT3 which deacetylates CypD is downregulated in AD [ 26 ]. Furthermore, oAβ-CypD complexes were found in AD brains and transgenic AD mice [ 27 , 28 ].…”

Section: Brain Disorder and Mitochondrial Dysfunctionmentioning

confidence: 99%

Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

et al. 2021

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The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

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“…NR1D1 is a key integrator of metabolism with the circadian clock and inhibits pro-inflammatory M1 macrophages and NLRP3 inflammasome activation ( 107 ). SIRT3 and PPAR-α play crucial roles in mitochondrial quality control, oxidative phosphorylation, and FAO in various cell types ( 108 , 109 ). Thus, TFEB, and its upstream signaling molecules, may orchestrate immunometabolism, autophagy, and the inflammatory response during Mtb infection.…”

Section: Tfeb: a Potential Coordinator Of Autophagy And Metabolism Dumentioning

confidence: 99%

An Interplay Between Autophagy and Immunometabolism for Host Defense Against Mycobacterial Infection

Paik

2020

Front. Immunol.

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Autophagy, an intracellular catabolic pathway featuring lysosomal degradation, is a central component of the host immune defense against various infections including Mycobacterium tuberculosis (Mtb), the pathogen that causes tuberculosis. Mtb can evade the autophagic defense and drive immunometabolic remodeling of host phagocytes. Co-regulation of the autophagic and metabolic pathways may play a pivotal role in shaping the innate immune defense and inflammation during Mtb infection. Two principal metabolic sensors, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) kinase, function together to control the autophagy and immunometabolism that coordinate the anti-mycobacterial immune defense. Here, we discuss our current understanding of the interplay between autophagy and immunometabolism in terms of combating intracellular Mtb, and how AMPK-mTOR signaling regulates antibacterial autophagy in terms of Mtb infection. We describe several autophagy-targeting agents that promote host antimicrobial defenses by regulating the AMPK-mTOR axis. A better understanding of the crosstalk between immunometabolism and autophagy, both of which are involved in host defense, is crucial for the development of innovative targeted therapies for tuberculosis.

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Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

Cited by 289 publications

References 200 publications

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

An Interplay Between Autophagy and Immunometabolism for Host Defense Against Mycobacterial Infection

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