SIRT1 and aging related signaling pathways

Mechanisms of Ageing and Development, Journal Year: 2020, Volume and Issue: 187, P. 111215 - 111215

Published: Feb. 19, 2020

Language: Английский

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PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 20

Published: March 9, 2020

Peroxisome proliferator-activated receptor- γ coactivator (PGC)-1 α is a transcriptional described as master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation reactive oxygen species detoxification. PGC-1 highly expressed in tissues with high energy demands, it clearly associated the pathogenesis metabolic syndrome its principal complications obesity, type 2 diabetes mellitus, cardiovascular disease, hepatic steatosis. We herein review molecular pathways regulated by , which connect stress metabolism inflammatory response syndrome. regulates expression antioxidant genes, manganese superoxide dismutase, catalase, peroxiredoxin 3 5, uncoupling protein 2, thioredoxin reductase thus prevents injury dysfunction. Dysregulation alters redox homeostasis cells exacerbates response, commonly accompanied disturbances. During inflammation, low levels downregulate gene expression, induce stress, promote nuclear factor kappa B activation. In syndrome, characterized chronic grade dysregulation modifies properties altering function promoting accumulation. conclusion, acts an essential node connecting regulation, control, pathways, interesting therapeutic target that may have significant benefits for number diseases.

Language: Английский

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Betaine in Inflammation: Mechanistic Aspects and Applications

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: May 24, 2018

Betaine is known as trimethylglycine (TMG) and widely distributed in animals, plants microorganisms. to function physiologically an important osmoprotectant methyl group donor. Accumulating evidence has shown that betaine anti-inflammatory functions numerous diseases. Mechanistically, ameliorates sulfur amino acid (SAA) metabolism against oxidative stress, inhibits nuclear factor-κB (NF-κB) activity NLRP3 inflammasome activation, regulates energy metabolism, mitigates endoplasmic reticulum (ER) stress apoptosis. Consequently, beneficial actions several human diseases, such obesity, diabetes, cancer Alzheimer’s disease.

Language: Английский

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Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 793 - 793

Published: July 30, 2019

The importance of reactive oxygen species (ROS) has been gradually acknowledged over the last four decades. Initially perceived as unwanted products detrimental oxidative stress, they have upgraded since, and now ROS are also known to be essential for regulation physiological cellular functions through redox signaling. In majority cases, metabolic demands, along with other stimuli, vital formation their actions. this review, we focus on role in regulating cell functioning communication among themselves. relevance therapy concepts is addressed here.

Language: Английский

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Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

Nature Reviews Molecular Cell Biology, Journal Year: 2017, Volume and Issue: 18(10), P. 595 - 609

Published: Aug. 9, 2017

Language: Английский

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Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure

CNS Neuroscience & Therapeutics, Journal Year: 2019, Volume and Issue: 25(7), P. 816 - 824

Published: March 19, 2019

Mitochondria not only supply the energy for cell function, but also take part in signaling. This review describes dysfunctions of mitochondria aging and neurodegenerative diseases, signaling pathways leading to mitochondrial biogenesis (including PGC-1 family proteins, SIRT1, AMPK) mitophagy (parkin-Pink1 pathway). Understanding regulation these may be beneficial finding pharmacological approaches or lifestyle changes (caloric restrict exercise) modulate and/or activate removal damaged mitochondria, thus reducing onset severity diseases.

Language: Английский

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CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(1), P. 157 - 173.e7

Published: May 30, 2019

Language: Английский

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Mitochondria–Lysosome Crosstalk: From Physiology to Neurodegeneration

Trends in Molecular Medicine, Journal Year: 2019, Volume and Issue: 26(1), P. 71 - 88

Published: Nov. 29, 2019

The functions of mitochondria and lysosomes are coordinated with cellular metabolism signaling.AMPK mTORC1 mediate mitochondria–lysosome crosstalk.Acute chronic mitochondrial stress has opposite effects on lysosomal biogenesis.Lysosomal storage diseases trigger repression biogenesis.Mitochondria–lysosome crosstalk is impaired in neurodegenerative diseases. Cellular function requires coordination between different organelles metabolic cues. Mitochondria essential for as major contributors chemical energy building blocks. It therefore pivotal to coordinate the roles lysosomes. However, these do more than metabolism, given their fundamental signaling platforms cell that regulate many key processes such autophagy, proliferation, death. Mechanisms discussed, both under physiological conditions affect organelles. Life an elaborate system reactions which require organization. This chemistry often compartmentalized by phases or physical barriers. mitochondria, peroxisomes, lysosomes, others present extreme examples compartmentalization containing a specific set within limits membranes. These carry out together contribute survival cell, eventually its growth division. provided presents, however, challenge cell: must be ensure whole tuned. Multicellular organisms have types, but they all common aspects use ATP thioester bonds currency, well ability survive stresses (e.g., ischemia-induced hypoxia, fever-related heat shock). Cells cope triggering appropriate responder, triggers carefully executed plan adaptation survival. One met almost cells availability nutrients energy, lack thereof. Metabolism component responses because it allows redirection fuels generate (catabolism) conversion into blocks (anabolism). Both branches rely heavily not only providers also regulators activity across cell. Therefore, effectively coordinated. purpose this review discuss recent advances understanding communication how contributes function, perturbations involved pathology. Although outcomes conserved higher lower Eukarya, underlying mechanisms differ significantly. We focus mammalian crosstalk. To organelles, several need controlled: when organelle built (biogenesis), where positioned, performs, removed. Reciprocally, inform status needs, needs react accordingly. kinetics any may respond particular seconds minutes nutrient depletion, exercise, activation immune cells) remain long time infection, genetic defects organelle). Organelle biogenesis used reference transcriptional programs expression complete repertoire proteome, leading import assembly those proteins macromolecular complexes organelle. In review, refers programs. described Box 1, important note transcription factors seem able biogenesis.Box 1Mitochondrial Lysosomal BiogenesisThe comprise genes necessary make functional new complex involve ∼600 [98Palmieri M. et al.Characterization CLEAR network reveals integrated control clearance pathways.Hum. Mol. Genet. 2011; 20: 3852-3866Crossref PubMed Scopus (325) Google Scholar] ∼1000–1500 [99Pagliarini D.J. al.A protein compendium elucidates I disease biology.Cell. 2008; 134: 112-123Abstract Full Text PDF (1194) Scholar]. Specific cis-elements promoters enhancers drive expression.Multiple promote biogenesis, nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor α (PPAR-α), PPAR-β/δ, PPAR-γ, estrogen-related (ERRα), ERRγ, Myc, 2 (known GA-binding factor, composed β subunits, GABPA GABPB; NRF2 should avoided unrelated erythroid 2-like 2, NFE2L2, coordinates antioxidant responses) examples. Many other been implicated some genes, less clear whether can entire program SP1, MEF2, CREB, FoxO, YY-1, E2F1, among others. promoting work association coactivators PGC-1α PGC-1β. A comprehensive discussion outside scope article summarized elsewhere [100Quiros P.M. al.Mitonuclear homeostasis stress.Nat. Rev. Cell Biol. 2016; 17: 213-226Crossref (192) Notably, although known activate two were recently found repress biogenesis. KLF2 ETV1 silence nucleus-encoded overexpression results impairment chain [42Yambire K.F. al.Mitochondrial transcriptionally repressed lipid diseases.eLife. 2019; 8: e39598Crossref (1) Scholar].The (nucleus-encoded encode proteins) ensured microphthalmia TFEB, MITF, TFE3, TFEC [101Sardiello gene regulating function.Science. 2009; 325: 473-477Crossref (943) coactivator ACSS2 cooperates TFEB [102Li X. al.Nucleus-translocated promotes autophagy.Mol. Cell. 2017; 66: 684-697Abstract (47) Other induce PPARα, E2F1 [103Fullgrabe J. al.Transcriptional regulation autophagy at glance.J. Sci. 129: 3059-3066Crossref (35) Several autophagy-related same regulatory circuits genes. As case there negative lysosomal/autophagy farnesoid X (FXR) bromodomain BRD4 Scholar].Interestingly, influence E2F1. remains unclear simultaneously, evidence TFE3 lines vivo [104Pastore N. al.TFE3 regulates whole-body cooperation TFEB.EMBO Med. 9: 605-621Crossref (16) Scholar], possibly involving induction PGC1α, coordinator (and peroxisomal) [105Wu Z. al.Mechanisms controlling respiration through thermogenic PGC-1.Cell. 1999; 98: 115-124Abstract (2571) represent mechanism peroxisomes). expression. Multiple Interestingly, positioning overlooked issue. There populations positions relative plasma membrane nucleus [1Korolchuk V.I. al.Lysosomal responses.Nat. 13: 453-460Crossref (393) are, normal conditions, spread around relatively uniform manner, rapidly relocate perinuclear region onset [2De Paepe B. al.Fluorescence imaging cultured skin fibroblasts: useful method detection oxidative phosphorylation defects.Pediatr. Res. 2012; 72: 232-240Crossref (8) Scholar,3Al-Mehdi A.B. al.Perinuclear clustering creates oxidant-rich domain required hypoxia-induced transcription.Sci. Signal. 5: ra47Crossref (156) Importantly, distribution considered importance interactions contact sites) fission) Ca2+ homeostasis, cholesterol trafficking, phospholipid synthesis [4Scorrano L. al.Coming define sites.Nat. Commun. 10: 1287Crossref (17) role sites discussed later article. constantly rest using multiple strategies. referred 'retrograde' originate nucleus, opposed 'anterograde' machinery modulates [5Raimundo signaling.in: Hockenberry D.M. Death. Humana Press, 2015: 169-184Google For example, retain calcium (Ca2+), iron, cholesterol, sphingomyelin, each sensed [6Perera R.M. Zoncu R. lysosome hub.Annu. Dev. 32: 223-253Crossref relay increasing/decreasing uptake, slowing down import, releasing metabolites, reactive oxygen species (ROS), vesicles, exporting peptides (such ClpP- HAF-1-dependent peptide export C. elegans proteotoxic MOTS-c mammals) DNA (mtDNA) [7Pellegrino M.W. al.Signaling unfolded response.Biochim. Biophys. Acta. 2013; 1833: 410-416Crossref (176) Scholar,8West A.P. primes antiviral innate response.Nature. 2015; 520: 553-557Crossref (89) paradigm, retrograde depends properties signal: trigger, intensity, frequency, duration. duration signal aspect acute remarkably different, least [9Raimundo Mitochondrial pathology: signals from factory.Trends 2014; 282-292Abstract (66) determinants termination. occasions cessation normoxia after hypoxic conditions) sufficient remove signal, termination achieved removal perturbed damaged maintenance healthy organellar function. strategies place recognize eliminate typically selective (mitophagy) (lysophagy). manner defective recognized differs 'red flag' seems depolarization, diverse ubiquitination outer membrane, recruitment mitophagy receptors, delivery mitochondria-containing autophagosomes degradation [10Youle R.J. Narendra D.P. mitophagy.Nat. 12: 9-14Crossref (1490) main event demise rupture, exposure parts glycocalyx galectin family proteins, then ruptured [11Jia al.Galectins mTOR response endomembrane damage.Mol. 2018; 70: 120-135Abstract (28) detailed lysophagy comprehensively reviews. interdependence underscored obtained malfunction. mouse embryonic fibroblasts lacking AIFM1 (apoptosis-inducible factor), OPA1, fusion, PINK1, quality mitophagy, show [12Demers-Lamarche al.Loss impairs lysosomes.J. Chem. 291: 10263-10276Crossref (57) evidenced enlargement (LAMP1-positive) become nonacidic lose hydrolytic detrimental effect dysfunction constant types vitro clonal lines) effector T cells, Huntington's heart) [13Baixauli F. controls during inflammatory responses.Cell Metab. 22: 485-498Abstract Scholar, 14Fernandez-Mosquera deficiency inhibits hydrolysis.Autophagy. 15: 1572-1591Crossref (3) 15Joshi A.U. al.Drp1/Fis1-mediated fragmentation leads cardiac models disease.J. Cardiol. 127: 125-133Abstract (0) 16Padman B.S. al.The protonophore CCCP interferes autophagic cargo yeast cells.Autophagy. 1862-1875Crossref does related decreased 13Baixauli mentioned above, increase similar paradigm observed function: (transcription EB) activated Scholar,17Fernandez-Mosquera al.Acute differentially biogenesis.Sci. Rep. 7: 45076Crossref 18Ivankovic D. following PINK1/parkin-mediated mitophagy.J. Neurochem. 136: 388-402Crossref 19Nezich C.L. al.MiT/TFE downstream Parkin Atg5.J. 210: 435-450Crossref occurs stress, [17Fernandez-Mosquera was pharmacologic inhibition high first hours inhibition, returned basal levels, actively inhibited persisted over 24 h (TFAM) protein, maintenance, transcription, replication mtDNA, upregulated Nevertheless, determined TFEB-dependent, what is, Tfam−/− still dysfunctional Furthermore, even classic biogenesis-stimulating amino acid starvation [14Fernandez-Mosquera Considering general picture emerges gears whereas shut inhibited. interpreted that, ultimately result elimination stimulating autophagosome formation, ensuring capacity increased occur indefinitely, would run constitute threat life most types. Thus, period 'clean-up' mode on, prefers inhibiting formation – better live unable efficiently phosphorylation, no irreversibly impair phospholipids, heme, Fe–S clusters. underlie uncovered. triggered factors, particularly exactly ones likely dependent type AMPK (AMP-dependent kinase) activation, [20Young N.P. al.AMPK governs lineage specification Tfeb-dependent lysosomes.Genes 30: 535-552Crossref (37) sensor charge [21Garcia Shaw AMPK: Sensing restoration balance.Mol. 789-800Abstract grand regulator activates catabolic pathways while anabolism. counterbalance mTORC1, kinase anabolic pathways. interplay brief int

Language: Английский

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Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy

Circulation, Journal Year: 2021, Volume and Issue: 144(21), P. 1714 - 1731

Published: Oct. 21, 2021

Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating structure-function relationships, there still much be learned about mechanisms that link altered cardiac energetics phenotypes. In this work, we test hypothesis changes represent common pathophysiologic pathway HCM.

Language: Английский

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Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(4), P. 735 - 753.e4

Published: Oct. 1, 2019

Language: Английский

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