An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus cen...An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus central to the process whereby organisms adapt to their respective environments.Mitochondria produce molecular energy via oxidative phosphorylation that then allows cells to biosynthetically respond and adapt to changes in their environment.Reactive oxygen species(ROS)are by-products of oxidative phosphorylation that can be either beneficial or damaging,depending on the context;ROS are hence both the conveyors of environmental stress as well as cellular“adaptogens”.Mitohormesis refers to the process whereby low levels of oxidative stress spur survival adaptations,whereas excessive levels stymie survival.Low energy and frequency pulsing electromagnetic fields have been recently shown capable of stimulating mitochondrial respiration and ROS production and instilling mitohormetic survival adaptations,similarly to,yet independently of,exercise,opening avenues for the future development of Magnetic Mitohormetic interventions for the improvement of human health.This viewpoint explores the possibilities and nuances of magnetic-based therapies as a form of clinical intervention to non-invasively activate magnetic mitohormesis for the management of chronic diseases.展开更多
Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and...Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for signaling.Causal mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron disease.Furthermore,lipid dysmetabolism within the central nervous system and circulation is associated with ALS.Here,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis.Among the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor neurons.We end with exploring the potential ALS therapeutics by reducing these toxic lipids.展开更多
In a recent study published in Cel^(l),Piperni and colleagues revealed that Blastocystis prevalence varies significantly across geographic regions and lifestyles,with higher carriage linked to healthier plant-based di...In a recent study published in Cel^(l),Piperni and colleagues revealed that Blastocystis prevalence varies significantly across geographic regions and lifestyles,with higher carriage linked to healthier plant-based diets and favorable cardiometabolic profiles.These findings position Blastocystis as a potential biomarker for gut health and metabolic well-being,challenging its traditional perception as a pathogen(Fig.1).展开更多
Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the pentose phosphate pathway(PPP)in glycolysis.Glucose metabolism is closely implicated in the regulation of mitophagy,a selective form of autopha...Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the pentose phosphate pathway(PPP)in glycolysis.Glucose metabolism is closely implicated in the regulation of mitophagy,a selective form of autophagy for the degradation of damaged mitochondria.The PPP and its key enzymes such as G6PD possess important metabolic functions,including biosynthesis and maintenance of intracellular redox balance,while their implication in mitophagy is largely unknown.Here,via a whole-genome CRISPR-Cas9 screening,we identified that G6PD regulates PINK1(phosphatase and tensin homolog[PTEN]-induced kinase 1)-Parkinmediated mitophagy.The function of G6PD in mitophagy was verified via multiple approaches.G6PD deletion significantly inhibited mitophagy,which can be rescued by G6PD reconstitution.Intriguingly,while the catalytic activity of G6PD is required,the known PPP functions per se are not involved in mitophagy regulation.Importantly,we found a portion of G6PD localized at mitochondria where it interacts with PINK1.G6PD deletion resulted in an impairment in PINK1 stabilization and subsequent inhibition of ubiquitin phosphorylation,a key starting point of mitophagy.Finally,we found that G6PD deletion resulted in lower cell viability upon mitochondrial depolarization,indicating the physiological function of G6PD-mediated mitophagy in response to mitochondrial stress.In summary,our study reveals a novel role of G6PD as a key positive regulator in mitophagy,which bridges several important cellular processes,namely glucose metabolism,redox homeostasis,and mitochondrial quality control.展开更多
Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed...Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed by lysine methyltransferase G9a,which functions as a heteromeric complex with G9a-like protein(GLP).G9a/GLP has other non-histone substrates,including itself.G9a/GLP is implicated in regulating synaptic plasticity,learning and memory[2,3].展开更多
基金supported by Lee Kong Chian MedTech Initiative,Singapore(N-176-000-045-001)the Institute for Health Innovation&Technology,iHealthtech,at the National University of Singaporefunded by Lee Kong Chian MedTech Initiative,Singapore.
文摘An organism’s survival depends on its ability to adapt to stress.Mitochondria are the cellular integrators of environmental stressors that ultimately translate their responses at the organismal level,and are thus central to the process whereby organisms adapt to their respective environments.Mitochondria produce molecular energy via oxidative phosphorylation that then allows cells to biosynthetically respond and adapt to changes in their environment.Reactive oxygen species(ROS)are by-products of oxidative phosphorylation that can be either beneficial or damaging,depending on the context;ROS are hence both the conveyors of environmental stress as well as cellular“adaptogens”.Mitohormesis refers to the process whereby low levels of oxidative stress spur survival adaptations,whereas excessive levels stymie survival.Low energy and frequency pulsing electromagnetic fields have been recently shown capable of stimulating mitochondrial respiration and ROS production and instilling mitohormetic survival adaptations,similarly to,yet independently of,exercise,opening avenues for the future development of Magnetic Mitohormetic interventions for the improvement of human health.This viewpoint explores the possibilities and nuances of magnetic-based therapies as a form of clinical intervention to non-invasively activate magnetic mitohormesis for the management of chronic diseases.
基金National Medical Research Council(NMRC/OFIRG/0042/2017)National Research Foundation(NRF2019-NRF-ISF003-3221)Ministry of Education(MOE-T2EP30220-0029),Singapore to S.-C.L.
文摘Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and sterols.Lipids not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for signaling.Causal mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron disease.Furthermore,lipid dysmetabolism within the central nervous system and circulation is associated with ALS.Here,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis.Among the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor neurons.We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
基金supported by European Cooperation in Science&Technology(EUCOST)grant(OC-2021-1-25116)awarded for Blastocystis under One Health'from the European Union(2022-2026)as well as by the Yong Loo Lin School of Medicine,National University of Singapore,through grant numbers A-8000685-00-00 and A-8000629-00-00 awarded to L.D.and K.S.-W.T.
文摘In a recent study published in Cel^(l),Piperni and colleagues revealed that Blastocystis prevalence varies significantly across geographic regions and lifestyles,with higher carriage linked to healthier plant-based diets and favorable cardiometabolic profiles.These findings position Blastocystis as a potential biomarker for gut health and metabolic well-being,challenging its traditional perception as a pathogen(Fig.1).
基金supported by grants to S.C.L.from the Swee Liew-Wadsworth Endowment fund,National University of Singapore(NUS),Ministry of Education(MOE-T2EP30220-0014),Singaporethe National Research Foundation(NRF-ISF003-3221),Singapore+2 种基金grants to H.M.S.from University of Macao(CPG2023-0032FHS and UM-MYRG2020-00022-FHS)Macao Science and Technology Development Fund(FDCT0078/2020/A2,FDCT0031/2021/A1,FDCT0081/2022/AMJ,and FDCT 0004/2021/AKP)supported by the NUS Graduate School Research Scholarships.
文摘Glucose-6-phosphate dehydrogenase(G6PD)is the rate-limiting enzyme in the pentose phosphate pathway(PPP)in glycolysis.Glucose metabolism is closely implicated in the regulation of mitophagy,a selective form of autophagy for the degradation of damaged mitochondria.The PPP and its key enzymes such as G6PD possess important metabolic functions,including biosynthesis and maintenance of intracellular redox balance,while their implication in mitophagy is largely unknown.Here,via a whole-genome CRISPR-Cas9 screening,we identified that G6PD regulates PINK1(phosphatase and tensin homolog[PTEN]-induced kinase 1)-Parkinmediated mitophagy.The function of G6PD in mitophagy was verified via multiple approaches.G6PD deletion significantly inhibited mitophagy,which can be rescued by G6PD reconstitution.Intriguingly,while the catalytic activity of G6PD is required,the known PPP functions per se are not involved in mitophagy regulation.Importantly,we found a portion of G6PD localized at mitochondria where it interacts with PINK1.G6PD deletion resulted in an impairment in PINK1 stabilization and subsequent inhibition of ubiquitin phosphorylation,a key starting point of mitophagy.Finally,we found that G6PD deletion resulted in lower cell viability upon mitochondrial depolarization,indicating the physiological function of G6PD-mediated mitophagy in response to mitochondrial stress.In summary,our study reveals a novel role of G6PD as a key positive regulator in mitophagy,which bridges several important cellular processes,namely glucose metabolism,redox homeostasis,and mitochondrial quality control.
基金This study was performed in accordance with the ethical review and received approval from the Institutional Animal Care and Use Committee(IACUC)of the National University of Singapore(IACUC protocol number:R16-0135).
文摘Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed by lysine methyltransferase G9a,which functions as a heteromeric complex with G9a-like protein(GLP).G9a/GLP has other non-histone substrates,including itself.G9a/GLP is implicated in regulating synaptic plasticity,learning and memory[2,3].
