Loss of NAD-Dependent Protein Deacetylase Sirtuin-2 Alters Mitochondrial Protein Acetylation and Dysregulates Mitophagy

Liu, Guoxiang; Park, Seong Hoon; Imbesi, Marta; Nathan, William Joseph; Zou, Xianghui; Zhu, Yueming; Jiang, Haiyan; Parisiadou, Loukia; Gius, David

doi:10.1089/ars.2016.6662

Cited by 120 publications

(98 citation statements)

References 47 publications

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“…Conversely, there is a reduction of PINK1 in CR mice, indicating that CR may attenuate mitochondrial damage. CR‐mediated autophagy that is dependent on SIRT1 increases mitophagy, whereas a loss of SIRT2 function leads to a dysregulation in mitophagy . AMPK is also implicated in mitophagy via the activation of Ulk1 …”

Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 99%

“…CR-mediated autophagy that is dependent on SIRT1 increases mitophagy, 87 whereas a loss of SIRT2 function leads to a dysregulation in mitophagy. 88 AMPK is also implicated in mitophagy via the activation of Ulk1. 34 CR decreases levels of ROS in the rat brain 89 and reduces the amount of oxidative damage to mitochondrial DNA in liver.…”

Section: Cr and Mitochondrial Healthmentioning

confidence: 99%

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Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

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Calorie intake is essential for regulating normal physiological processes and is fundamental to maintaining life. Indeed, both extremes of calorie intake result in increased morbidity and mortality. In this review, we discuss the effect of calorie intake on adult brain function, with an emphasis on the beneficial effects of mild calorie restriction.Recent findings relating to the regenerative and protective effects of the gastrointestinal hormone, ghrelin, suggest that it may underlie the beneficial effects of calorie restriction. We discuss the putative cellular mechanisms underlying the action of ghrelin and their possible role in supporting healthy brain ageing. K E Y W O R D Sacyl-ghrelin, adult hippocampal neurogenesis, calorie restriction, diet-induced obesity | INTRODUCTIONThe energy status of an organism is tightly controlled around a setpoint by hormonal and neural systems. These neuroendocrine checks and balances promote homeostasis, thereby ensuring an appropriate energy supply for the energetic demands of metabolism, physical activity, growth and repair.Disturbances to this homeostasis result in multiple physiological impairments, including age-related conditions such as type 2 dibetes mellitus and obesity. Perhaps less well recognised are the consequences of metabolic dysfunction on neuronal health and cognition.Diet-induced obesity (DIO) is a risk factor for neurodegenerative diseases such as Parkinson's disease (PD) and dementia. Conversely, calorie restriction (CR) (ie, an approximate 30% reduction in calorie intake) protects against neurodegeneration and promotes cognitive function (Figure 1). Indeed, there is a growing body of work supporting the CR paradigm as a tool for promoting lifespan and, perhaps more importantly, healthspan.1 However, the physiological mechanisms underlying these effects are not fully understood. Here, we review literature that identifies calorie intake as an important regulator of nerve cell function, with important implications for neurodegenerative disorders. Moreover, we describe recent research showing that CR promotes new neurone formation (neurogenesis) and neuroprotection in the adult brain and discuss the possible mechanisms that underpin this effect. | CALORIE RESTRICTION REGULATES BRAIN FUNCTIONCalorie restriction, in the absence of malnutrition, has beneficial effects on brain function, including reducing the incidence of age-related neurodegenerative disease, 2 eliciting anti-depressant behaviour 3 and improving memory function in rodents. 4 In nonhuman primates, prolonged CR in adulthood decreases the incidence of age-related disease, including measures of brain atrophy and glucose regulation. 5-7Translation of the carefully controlled CR experiments from preclinical models to humans is problematic. In particular, it is difficult to re-capitulate experimental controls such as genetic background and home environment (diet, temperature and lighting) that are standard in biomedical laboratory research. Nonetheless, in adult humans, a 3-month period of CR impr...

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Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 99%

Section: Cr and Mitochondrial Healthmentioning

confidence: 99%

Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

View full text Add to dashboard Cite

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“…However, multiple other signal transduction pathways are also involved in autophagy, including forkhead box protein O1, p38 mitogen-activated protein kinase, and Akt 2 (also known as RAC-β serine/threonine protein kinase) 221 . Importantly, autophagy and mitophagy are regulated by sirtuins, a family of NAD-dependent protein deacetylases 222–224 . Numerous studies have revealed a role for microRNAs (miRNAs) in the regulation of cardiac autophagy; some of these miRNAs are in the circulation or are delivered via exosomes 225–240 .…”

Section: Autophagy As a New Therapeutic Targetmentioning

confidence: 99%

New and revisited approaches to preserving the reperfused myocardium

et al. 2017

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Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.

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“…Therefore, deacetylation of specific substrates, (e.g., histones and transcriptional factors), occurs via the cofactor NAD 1 (Liu et al, 2015). Sirtuins also regulate fundamental biological processes, inclusive of glucose homeostasis, bioenergetic transduction, cell differentiation, and apoptosis (Liu et al, 2016a).…”

Section: Gsh and Disruptions Of Redox Homeostasismentioning

confidence: 99%

“…The presence of free cytosolic DNA leads to AIM2 inflammasome activation, and it has recently been demonstrated that mitochondria are a major source of DAMPs, which trigger neuroinflammatory responses resulting in apoptosis, pyroptosis, and autophagy (Liu et al, 2016a).…”

Section: Neuroinflammationmentioning

confidence: 99%

Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state

Calabrese

Giordano

Crupi

et al. 2016

J of Neuroscience Research

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Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes related to oxidative stress, oxidative damage to DNA, protein and lipids, as well as reduced glutathione levels in central and peripheral tissues could act synergistically, and contribute to the course of the disease. Herein, we discuss cellular mechanisms that may be operative in neuroinflammation and contributory to schizophrenia. We address modulation of endogenous cellular defense mechanisms as a potentially innovative approach to therapeutics for schizophrenia, and other neuropsychiatric conditions that are associated with neuroinflammation. Specifically, we discuss the emerging role of heme oxygenase as prominent member of neuroprotective network in redox stress responsive mechanisms, as well as the importance of glutathione relevant in schizophrenia pathophysiology. Finally we introduce the hormetic dose response concept as relevant and important to neuroprotection, and review hormetic mechanisms as possible approaches to manipulation of neuroinflammatory targets that may be viable for treating schizophrenia spectrum disorders. © 2016 Wiley Periodicals, Inc.

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Loss of NAD-Dependent Protein Deacetylase Sirtuin-2 Alters Mitochondrial Protein Acetylation and Dysregulates Mitophagy

Abstract: Together, these findings support that SIRT2 functions as a mitochondrial sirtuin, as well as a regulator of autophagy/mitophagy to maintain mitochondrial biology, thus facilitating cell survival. Antioxid. Redox Signal. 26, 849-863.

Cited by 120 publications

References 47 publications

Less is more: Caloric regulation of neurogenesis and adult brain function

Less is more: Caloric regulation of neurogenesis and adult brain function

New and revisited approaches to preserving the reperfused myocardium

Hormesis, cellular stress response and neuroinflammation in schizophrenia: Early onset versus late onset state

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