Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease

Neurotoxicity Research, Journal Year: 2023, Volume and Issue: 41(6), P. 708 - 729

Published: May 10, 2023

Language: Английский

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Pyruvate dehydrogenase fuels a critical citrate pool that is essential for Th17 cell effector functions

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112153 - 112153

Published: Feb. 26, 2023

Language: Английский

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The FASTK family proteins fine-tune mitochondrial RNA processing

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(11), P. e1009873 - e1009873

Published: Nov. 8, 2021

Transcription of the human mitochondrial genome and correct processing two long polycistronic transcripts are crucial for oxidative phosphorylation. According to tRNA punctuation model, nucleolytic these large precursor occurs mainly through excision tRNAs that flank most rRNAs mRNAs. However, some mRNAs not punctuated by tRNAs, it remains largely unknown how non-canonical junctions resolved. The FASTK family proteins emerging as key players in RNA processing. Here, we have generated cell lines carrying single or combined knockouts several members investigate their roles striking phenotypes were obtained with loss FASTKD4 FASTKD5 double knockout. Comprehensive transcriptome analyses revealed a defect at canonical junctions, accompanied an increase specific antisense transcripts. Loss led severe phenotype marked defects translation components electron transport chain complexes We reveal protein regulators junction non-coding

Language: Английский

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The Staphylococcus aureus CidA and LrgA Proteins Are Functional Holins Involved in the Transport of By-Products of Carbohydrate Metabolism

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 1, 2022

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA LrgA share with bacteriophage holins, we have hypothesized these function by forming pores within cytoplasmic membrane. To test this, utilized "lysis cassette" system demonstrated abilities cidA lrgA genes support endolysin-induced lysis. Typical CidA- LrgA-induced lysis was dependent coexpression endolysin, consistent proposed holin-like functions proteins. In addition, were shown localize surface membrane vesicles cause leakage small molecules, providing direct evidence their hole-forming potential. Consistent recent reports demonstrating role for homologues other bacterial plant species transport by-products carbohydrate metabolism, also show is important S. utilize pyruvate during microaerobic anaerobic growth, promoting uptake under conditions. Combined, data reveal possess properties play an metabolism. IMPORTANCE represent founding large, highly conserved span multiple kingdoms life. Despite fact they been PCD, very little known about molecular/biochemical encode. results presented this study functions, roles death. However, studies demonstrate are metabolic suggesting intriguing link between two seemingly disparate processes.

Language: Английский

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Thiophene-based organic dye with large Stokes shift and deep red emission for live cell NAD(P)H detection under varying chemical stimuli

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(27), P. 6296 - 6307

Published: Jan. 1, 2023

We report a novel method for synthesizing red and deep cyanine-based molecular probes with large Stokes shifts live cell NAD(P)H detection.

Language: Английский

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Efficacy of Astragalus membranaceus–Carthamus tinctorius in Cerebral Ischemia/Reperfusion Injury: Insights from Metabolomics and Mass Spectrometry Imaging

Phytomedicine, Journal Year: 2024, Volume and Issue: 133, P. 155881 - 155881

Published: July 15, 2024

Language: Английский

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Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 27, 2023

The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated is transported to neurons fuel metabolic processes required for long-term memory. Although studies in vertebrates have revealed shuttling important cognitive function, it uncertain if this form of coupling conserved invertebrates or influenced by age. Lactate dehydrogenase (Ldh) a rate limiting enzyme interconverts and pyruvate. Here we genetically manipulated expression Drosophila melanogaster (dLdh) glia assess the impact altered metabolism on invertebrate aging courtship memory at different ages. We also assessed survival, negative geotaxis, brain neutral lipids (the core component lipid droplets) metabolites. Both upregulation downregulation dLdh resulted decreased survival impairment with Glial caused age-related without altering while upregulated glial lowered disrupting neuronal increased accumulation. provide evidence age affects tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), Collectively, our findings indicate direct alteration either but only an age-dependent manner.

Language: Английский

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Role of Mitochondrial Transporters on Metabolic Rewiring of Pancreatic Adenocarcinoma: A Comprehensive Review

Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 411 - 411

Published: Jan. 8, 2023

Pancreatic cancer is among the deadliest cancers worldwide and commonly presents as pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming a hallmark of PDAC. Glucose glutamine metabolism are extensively rewired in order to fulfil both energetic synthetic demands this aggressive tumour maintain favorable redox homeostasis. The mitochondrial pyruvate carrier (MPC), (SLC1A5_Var), glutamate (GC), aspartate/glutamate (AGC), uncoupling protein 2 (UCP2) have all been shown influence PDAC cell growth progression. expression MPC downregulated its overexpression reduces rate, whereas other four transporters usually overexpressed loss one or more them renders cells unable grow proliferate by altering levels crucial metabolites such aspartate. aim review comprehensively evaluate current experimental evidence about function these carriers metabolic rewiring. Dissecting precise role context microenvironment necessary for targeted drug development.

Language: Английский

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Poly(ADP‐ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(6)

Published: March 18, 2024

Abstract PARP‐1 over‐activation results in cell death via excessive PAR generation different types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered Studies show that generated after can bind hexokinase‐1 (HK‐1) result glycolytic defects subsequent dysfunction. HK‐1 is the neuronal hexokinase catalyzes first reaction of glycolysis, converting glucose to glucose‐6‐phosphate (G6P), a common substrate for pentose phosphate pathway (PPP). PPP critical maintaining NADPH GSH levels G6P dehydrogenase activity. Therefore, will not only decrease bioenergetics but also cause imbalance due depletion GSH. In ischemia, whether PAR‐mediated inhibition known. We used oxygen–glucose deprivation (OGD) mouse cortical mimic ischemia cultures observed activation formation alters homeostasis neurons. pharmacological adenoviral‐mediated overexpression wild‐type (wtHK‐1) PAR‐binding mutant (pbmHK‐1). Our data or significantly improves homeostasis, survival exposed OGD. These suggest binding during OGD drive bioenergetic glycolysis impairment function.

Language: Английский

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Role of the OTAbZIP Gene in Regulating Growth and OTA Production in Aspergillus westerdijkiae fc-1 Under Osmotic Stress

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Background Ochratoxins are toxins primarily produced by fungi from the Aspergillus and Penicillium genera. Among these, Ochratoxin A (OTA) is most toxic exhibits strong carcinogenic effects. Reducing food contamination OTA a critical global challenge. Osmotic pressure an important environmental factor that regulates various metabolic pathways in Aspergillus westerdijkiae. It particularly affects HOG pathway, which controls fungal mycelium growth production. The OTAbZIP gene key transcription receptor A. plays vital role responding to osmotic regulating expression of biosynthesis genes (otaA-D). This study explored production under different conditions using RNA-Seq RT-qPCR analyses. Results Transcriptomic analysis showed influences several pathways. These include DNA replication, sugar metabolism, ribosome function, arginine proline metabolism at NaCl concentrations 0, 20, 100 g/L. Genes high osmolarity glycerol, mitogen-activated protein kinase (MAPK HOG) such as Hog1, Gpd1, Cdc28, Ctt1 were affected. ΔOTAbZIP mutant strain exhibited increased sensitivity stress. results confirmed was significantly lower than wild-type (WT) westerdijkiae fc-1. However, mutation did not affect activation Hog1 gene. Conclusions highlights linked findings enhance our understanding gene's functions fc-1 somatic pressures. They also offer insights for developing strategies control feed.

Language: Английский

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