Mitochondria: It is all about energy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

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Human cardiac metabolism

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(7), P. 1456 - 1481

Published: July 1, 2024

Language: Английский

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Lactate and lactylation in cardiovascular diseases: current progress and future perspectives

Metabolism, Journal Year: 2024, Volume and Issue: 158, P. 155957 - 155957

Published: June 21, 2024

Language: Английский

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Lactate and lactylation in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Language: Английский

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Lactate controls cancer stemness and plasticity through epigenetic regulation

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Tumors arise from uncontrolled cell proliferation driven by mutations in genes that regulate stem renewal and differentiation. Intestinal tumors, however, retain some hierarchical organization, maintaining both cancer cells (CSCs) differentiated (CDCs). This heterogeneity, coupled with cellular plasticity enabling CDCs to revert CSCs, contributes therapy resistance relapse. Using genetically encoded fluorescent reporters human tumor organoids, combined our machine-learning-based tracker, CellPhenTracker, we simultaneously traced cell-type specification, metabolic changes, reconstructed lineage trajectories during organoid development. Our findings reveal distinctive phenotypes CSCs CDCs. We find lactate regulates dynamics, suppressing CSC differentiation inducing dedifferentiation into a proliferative state. Mechanistically, increases histone acetylation, epigenetically activating MYC. Given lactate's regulation of MYC depends on the bromodomain-containing protein 4 (BRD4), targeting metabolism BRD4 inhibitors emerge as promising strategy prevent

Language: Английский

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Lactate infusion improves cardiac function in a porcine model of ischemic cardiogenic shock

Critical Care, Journal Year: 2025, Volume and Issue: 29(1)

Published: March 14, 2025

Cardiogenic shock (CS) is associated with high mortality and medical therapies have failed to improve survival. Treatment lactate improved cardiac function which may benefit this condition. Comprehensive hemodynamic assessment of administration in CS lacking, the mechanisms underlying cardiovascular effects not yet been elucidated. In study we aimed cardiometabolic treatment experimental ischemic CS. a randomized, blinded design, 20 female pigs (60 kg) were studied. Left main coronary artery microsphere injections used cause CS, defined as 30% reduction CO or mixed venous saturation (SvO2). Subjects randomized receive either intravenous exogenous euvolemic, equimolar saline (control) for 180 min. Positive inotropic control dobutamine was administered on top ongoing after Extensive measurements obtained from pulmonary left ventricular (LV) pressure–volume catheterization. Furthermore, endomyocardial biopsies analyzed mitochondrial arterial, renal vein, sinus blood samples collected. The primary endpoint change during min treatment. Arterial levels increased 2.4 ± 1.1 7.7 mmol/L (P < 0.001) infusion. by 0.7 L/min compared control, due stroke volume = 0.003). Notably, heart rate mean arterial pressure did differ significantly between treatments. End-systolic elastance (load independent contractility) enhanced infusion 0.048), together LV ejection fraction 0.009) dP/dt(max) 0.041). (afterload) 0.12). This resulted ventriculo-arterial coupling efficiency 0.012). Cardiac mechanical 0.003), diuresis 0.016), SvO2 0.018) Myocardial complex I respiration 0.04). Concomitant further improvements control. Lactate myocardial porcine model included mediated through increase. These favorable patients

Language: Английский

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Lactate metabolism in neurodegenerative diseases

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(1), P. 69 - 74

Published: April 13, 2023

Lactate, a byproduct of glycolysis, was thought to be metabolic waste until the discovery Warburg effect. Lactate not only functions as substrate provide energy but can also function signaling molecule modulate cellular under pathophysiological conditions. The Astrocyte-Neuron Shuttle has clarified that lactate plays pivotal role in central nervous system. Moreover, protein lactylation highlights novel regulating transcription, functions, and disease development. This review summarizes recent advances metabolism its neurodegenerative diseases, thus providing optimal perspectives for future research.

Language: Английский

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Wearable device for continuous sweat lactate monitoring in sports: a narrative review

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: April 4, 2024

In sports science, the use of wearable technology has facilitated development new approaches for tracking and assessing athletes’ performance. This narrative review rigorously explores evolution contemporary state devices specifically engineered continuously monitoring lactate levels in sweat, an essential biomarker appraising endurance Lactate threshold tests have traditionally been integral tailoring training intensity athletes, but these relied on invasive blood that are impractical outside a laboratory setting. The transition to noninvasive, real-time through introduces innovative approach, facilitating continuous assessment without constraints inherent traditional methodologies. We selected 34 products from pool 246 articles found meticulous search published up January 2024 renowned databases: PubMed, Web Science, ScienceDirect. used keywords such as “sweat monitoring,” “continuous “wearable devices.” findings underscore capabilities noninvasive sweat technologies conduct long-term assessments over broad range 0–100 mM, providing safer alternative with minimal infection risks. By enabling evaluations (LT) maximal steady (MLSS), offer athletes various device options tailored their specific preferences. mechanisms currently available technologies, focusing electrochemical sensors undergone extensive research show promise commercialization. These employ amperometric reactions quantify detect changes resulting enzymatic activities. contrast, colorimetric more straightforward user-friendly approach by displaying concentrations color alterations. Despite significant advancements, relationship between remains intricate owing factors environmental conditions lag exercise initiation sweating. Furthermore, there is marked gap compared across disciplines. highlights need further address shortcomings substantiate performance broader spectrum environments. tremendous potential supplant pioneer avenues athlete management optimization real-world settings heralds promising future integrating science technology.

Language: Английский

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Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle

Science Advances, Journal Year: 2024, Volume and Issue: 10(26)

Published: June 26, 2024

Once considered as a “metabolic waste,” lactate is now recognized major fuel for tricarboxylic acid (TCA) cycle. Our metabolic flux analysis reveals that skeletal muscle mainly uses to TCA Lactate transported through the cell membrane via monocarboxylate transporters (MCTs) in which MCT1 highly expressed muscle. We analyzed how affects functions using mice with specific deletion of enhances running performance, increases oxidative fibers while decreasing glycolytic fibers, and glucose deficiency expression mitochondrial proteins, augments respiration rate, elevates activity Mechanistically, protein level PGC-1α, master regulator biogenesis, elevated upon loss cellular NAD + SIRT1 activity. Collectively, these results demonstrate MCT1-mediated shuttle plays key role regulating by modulating biogenesis flux.

Language: Английский

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What Is the Role of Lactate in Brain Metabolism, Plasticity, and Neurodegeneration?

Neurology, Journal Year: 2024, Volume and Issue: 102(9)

Published: April 4, 2024

Language: Английский

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