Metabolic reprogramming of the inflammatory response in the nervous system: the crossover between inflammation and metabolism DOI Creative Commons
Jesús Amo‐Aparicio, Charles A. Dinarello, Rubèn López‐Vales

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(10), P. 2189 - 2201

Published: Dec. 21, 2023

Metabolism is a fundamental process by which biochemicals are broken down to produce energy (catabolism) or used build macromolecules (anabolism). has received renewed attention as mechanism that generates molecules modulate multiple cellular responses. This was first identified in cancer cells the Warburg effect, but it also present immunocompetent cells. Studies have revealed bidirectional influence of metabolism and immune cell function, highlighting significance metabolic reprogramming activation effector functions. Metabolic processes such glycolysis, oxidative phosphorylation, fatty acid oxidation been shown undergo dynamic changes during response, facilitating energetic biosynthetic demands. review aims provide better understanding occurs different upon activation, with special focus on central nervous system disorders. Understanding response not only provides insights into mechanisms regulate function opens new approaches for therapeutic strategies aimed at manipulating system.

Language: Английский

Calculation of ATP production rates using the Seahorse XF Analyzer DOI Creative Commons
Brandon R. Desousa, Kristen K.O. Kim, Anthony E. Jones

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(10)

Published: Aug. 7, 2023

Abstract Oxidative phosphorylation and glycolysis are the dominant ATP‐generating pathways in mammalian metabolism. The balance between these two is often shifted to execute cell‐specific functions response stimuli that promote activation, proliferation, or differentiation. However, measurement of metabolic switches has remained mostly qualitative, making it difficult discriminate healthy, physiological changes energy transduction compensatory responses due dysfunction. We therefore present a broadly applicable method calculate ATP production rates from oxidative using Seahorse XF Analyzer data empirical conversion factors. quantify bioenergetic observed during macrophage polarization as well cancer cell adaptation vitro culture conditions. Additionally, we detect substantive utilization upon neuronal depolarization T receptor activation not evident steady‐state measurements. This generates single readout allows direct comparison produced live cells. manuscript provides framework for tailoring calculations specific systems experimental

Language: Английский

Citations

35
Long-term super-resolution inner mitochondrial membrane imaging with a lipid probe DOI Creative Commons
Shuai Zheng, Neville Dadina, Deepto Mozumdar

et al.

Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 20(1), P. 83 - 92

Published: Oct. 19, 2023

Abstract The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control health cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N 3 use it assemble high-density environmentally sensitive (HIDE) probes that selectively label image IMM in live cells multiple states. pairs with strain-promoted azide–alkyne click chemistry-reactive fluorophores support HIDE imaging using confocal, structured illumination, single-molecule localization stimulated emission depletion microscopy, all significantly improved resistance photobleaching. These generate images excellent spatial temporal resolution, require no genetic manipulations, are non-toxic model lines primary cardiomyocytes (even under conditions amplify effects of toxins) can visualize for 12.5 h. This probe will enable comprehensive studies high resolution.

Language: Английский

Citations

30
Hypermetabolism and energetic constraints in mitochondrial disorders DOI
Alexander J. Sercel, Gabriel Sturm, Dympna Gallagher

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(2), P. 192 - 195

Published: Feb. 9, 2024

Language: Английский

Citations

17
Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency DOI
Haoming Wang, John Vant, Andrew Zhang

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(9), P. 1712 - 1735

Published: Sept. 11, 2024

Language: Английский

Citations

11
IL-15 reprogramming compensates for NK cell mitochondrial dysfunction in HIV-1 infection DOI Creative Commons
Elia Moreno-Cubero, Aljawharah Alrubayyi, Štefan Bálint

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(4)

Published: Jan. 16, 2024

Dynamic regulation of cellular metabolism is important for maintaining homeostasis and can directly influence immune cell function differentiation, including NK responses. Persistent HIV-1 infection leads to a state chronic activation, subset redistribution, progressive dysregulation. In this study, we examined the metabolic processes that characterize subsets in infection, adaptive subpopulations expressing activating receptor NKG2C, which expand during infection. These cells exhibit an enhanced profile HIV-1- individuals infected with human cytomegalovirus (HCMV). However, bioenergetic advantage CD57+NKG2C+ diminished where uniformly display reduced oxidative phosphorylation (OXPHOS). Defective OXPHOS was accompanied by increased mitochondrial depolarization, structural alterations, DRP-1 levels promoting fission, suggesting defects are restricting plasticity The requirement response stimulation alleviated upon IL-15 pretreatment, mammalian target rapamycin complex 1 (mTORC1) activity. priming functionality anti-CD16 representing effective strategy pharmacologically boosting

Language: Английский

Citations

8
The Warburg Effect is the result of faster ATP production by glycolysis than respiration DOI Creative Commons
Matthew A. Kukurugya, Saharon Rosset, Denis V. Titov

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(46)

Published: Nov. 8, 2024

Many prokaryotic and eukaryotic cells metabolize glucose to organism-specific by-products instead of fully oxidizing it carbon dioxide water—a phenomenon referred as the Warburg Effect. The benefit a cell is not understood, given that partial metabolism yields an order magnitude less adenosine triphosphate (ATP) per molecule than complete oxidation. Here, we test previously formulated hypothesis Effect increase ATP production rate by switching from high-yielding respiration faster glycolysis when excess available becomes limited proteome occupancy. We show produces gram pathway protein in Escherichia coli , Saccharomyces cerevisiae mammalian cells. then develop simple mathematical model energy uses five experimentally estimated parameters this can accurately predict absolute rates all three organisms under diverse conditions, providing strong support for validity maximization hypothesis. In addition, our measurements up 10-fold slower E. or S. suggesting highly evolvable trait heavily optimized microbes. also find fermentation, explaining observation unlike cells, never switch pure fermentation presence oxygen.

Language: Английский

Citations

8
Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation DOI Creative Commons
Andréa B. Ball, Anthony E. Jones,

Kaitlyn B. Nguyễn

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

1
Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques DOI Open Access
Danielle E. Levitt, Brianna Bourgeois,

Keishla M. Rodríguez‐Graciani

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2448 - 2448

Published: Feb. 19, 2024

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. hypothesized short-term CBA/SIV would synergistically decrease impair bioenergetic parameters in female Myoblasts from naïve (CBA-/SIV-), vehicle [VEH]/SIV, (N = 4-6/group) groups were proliferated (3 days) differentiated (5 0 50 mM ethanol (short-term). decreased increased non-mitochondrial oxygen consumption rate (OCR) versus and/or VEH/SIV. Short-term differentiation; maximal OCR, mitochondrial reactive species (ROS) production, aldolase activity; glycolytic measures, ATP membrane potential (ΔΨm), pyruvate kinase activity. Mitochondrial ROS production was closely associated network volume, indices key health function parameters. Results indicate CBA non-synergistically myoblast capacity. impaired function, driving the deficit. suggest potentially differing mechanisms underlying CBA, highlighting need to elucidate impact different use patterns on

Language: Английский

Citations

4
MYC is a regulator of androgen receptor inhibition-induced metabolic requirements in prostate cancer DOI Creative Commons

Preston D. Crowell,

Jenna M. Giafaglione, Anthony E. Jones

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(10), P. 113221 - 113221

Published: Oct. 1, 2023

Advanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical understand how tumor cells inhibition in order exploit therapy-induced phenotypes prior outgrowth of treatment-resistant disease. Here, we comprehensively characterize effects blockade on cancer metabolism using transcriptomics, metabolomics, and bioenergetics approaches. The metabolic response defined by reduced glycolysis, robust elongation mitochondria, increased reliance mitochondrial oxidative metabolism. We establish DRP1 activity MYC as mediators AR-blockade-induced phenotypes. Rescuing phosphorylation after restores fission, while rescuing glycolytic prevents sensitivity complex I inhibition. Our study provides insight into regulation treatment-induced vulnerabilities cancer.

Language: Английский

Citations

9
Identification of biomarkers associated with ferroptosis in macrophages infected with Mycobacterium abscessus using bioinformatic tools DOI Creative Commons

Jiahua Qian,

Chenghua Lu, Kai Meng

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314114 - e0314114

Published: Jan. 10, 2025

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium that causes severe pulmonary infections. Recent studies indicate ferroptosis may play critical role in the pathogenesis of M . disease. We obtained gene expression microarray data from Gene Expression Omnibus database, focusing on THP-1-derived macrophages infected with and uninfected controls. Differentially expressed genes related to were identified through weighted co-expression network analysis "limma" package, followed by set variation enrichment for assessment. To explore regulatory relationships among hub genes, we constructed RBP-mRNA, ceRNA, TF-mRNA networks. Additionally, protein-protein interaction was built, functional analyses conducted genes. The diagnostic value these assessed using receiver operating characteristic curves. Six differentially associated infection. curves demonstrated had excellent predictive Functional showed involved immune responses, inflammation, cellular metabolism, cell death, apoptosis. Pathway revealed significant pathways apoptosis, hypoxia. RBP-mRNA highlighted interactions between key RNA-binding proteins, while ceRNA predicted miRNAs lncRNAs regulate ferroptosis-related NACC2 ITPKB Furthermore, HSD3B7 transcription factors LMNB1 ASCL1 promote influencing iron metabolism reactive oxygen species production, contributing infection process. Our findings biomarkers linked infection, providing new insights into its pathogenic mechanisms potential therapeutic strategies.

Language: Английский

Citations

0