Mitochondrial signal transduction

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1620 - 1653

Published: Nov. 1, 2022

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue the processor cell, together with nucleus other they constitute mitochondrial information processing system (MIPS). In a three-step process, (1) sense respond to both endogenous environmental inputs through morphological functional remodeling; (2) integrate network-based physical interactions diffusion mechanisms; (3) produce output signals tune functions systemically regulate physiology. This input-to-output transformation allows metabolic, biochemical, neuroendocrine, local or systemic enhance organismal adaptation. An explicit focus on signal transduction emphasizes role communication in biology. framework also opens new avenues understand how mediate inter-organ processes underlying human health.

Language: Английский

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Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(4), P. 546 - 562

Published: April 26, 2023

Language: Английский

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Pleiotropic effects of mitochondria in aging

Nature Aging, Journal Year: 2022, Volume and Issue: 2(3), P. 199 - 213

Published: March 17, 2022

Language: Английский

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Blood mitochondrial DNA copy number: What are we counting?

Mitochondrion, Journal Year: 2021, Volume and Issue: 60, P. 1 - 11

Published: June 19, 2021

Language: Английский

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Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

Current Environmental Health Reports, Journal Year: 2022, Volume and Issue: 9(4), P. 631 - 649

Published: July 28, 2022

Abstract Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences extend beyond the cell. already susceptible to damage, which be exacerbated by environmental exposures. Therefore, aim this review is summarize recent literature (2012–2022) looking at effects six ubiquitous classes compounds on in human populations. Recent Findings The suggests there a number biomarkers commonly used identify dysfunction, each with certain advantages limitations. Classes toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, nanomaterials can damage mitochondria varied ways, changes mtDNA copy measures oxidative most measured Other include membrane potential, calcium levels, ATP levels. Summary This identifies characterize but emerging biomarkers, cell-free blood cardiolipin provide greater insight into impacts exposures function. using novel approaches addition well-characterized ones create standardized protocols. We identified dearth studies populations exposed chemicals, nanoparticles gap knowledge needs attention.

Language: Английский

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Mitochondria-derived cell-to-cell communication

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112728 - 112728

Published: July 1, 2023

In addition to their intracellular mobility, mitochondria and components can exist outside the cells from which they originate. As a result, are capable of acting on non-parental distant mediate intercellular communication in physiological conditions variety pathologies. It has recently been demonstrated that this horizontal transfer governs wide range biological processes, such as tissue homeostasis, rescue injured recipient cells, tumorigenesis. addition, due mitochondria's bacterial ancestry, be recognized damage-associated molecular patterns (DAMPs) by immune leading inflammation. Here, we provide an overview most current significant findings concerning different structures extracellular by-products functions pathological context. This account illustrates ongoing expansion our understanding role mammalian organisms.

Language: Английский

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Recommendations for mitochondria transfer and transplantation nomenclature and characterization

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

Published: Jan. 16, 2025

Language: Английский

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Static lung storage at 10°C maintains mitochondrial health and preserves donor organ function

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(611)

Published: Sept. 15, 2021

Cold static preservation on ice (~4°C) remains the clinical standard of donor organ preservation. However, mitochondrial injury develops during prolonged storage, which limits extent time that organs can maintain viability. We explored feasibility lung storage at 10°C using a large animal model and investigated mechanisms related to protection. Functional assessments performed ex vivo perfusion demonstrated porcine lungs stored for 36 hours had lower airway pressures, higher compliances, better oxygenation capabilities, indicative pulmonary physiology, as compared conventionally 4°C. Mitochondrial protective metabolites including itaconate, glutamine, N-acetylglutamine were present in greater intensities than Analysis markers further confirmed resulted protection health. applied this strategy clinically prolong human beyond currently accepted limit about 6 8 hours. Five patients received transplants after median 10.4 (9.92 14.8 hours) first implanted 12.1 (10.9 16.5 second. All have survived 30 days transplantation. There was no grade 3 primary graft dysfunction 72 transplantation, post-transplant mechanical ventilation 1.73 (0.24 6.71 days). Preservation could become care preservation, providing benefits both health teams.

Language: Английский

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New Perspectives on the Importance of Cell-Free DNA Biology

Diagnostics, Journal Year: 2022, Volume and Issue: 12(9), P. 2147 - 2147

Published: Sept. 3, 2022

Body fluids are constantly replenished with a population of genetically diverse cell-free DNA (cfDNA) fragments, representing vast reservoir information reflecting real-time changes in the host and metagenome. As many body can be collected non-invasively one-off serial fashion, this tapped to develop assays for diagnosis, prognosis, monitoring wide-ranging pathologies, such as solid tumors, fetal genetic abnormalities, rejected organ transplants, infections, potentially others. The translation cfDNA research into useful clinical tests is gaining momentum, recent progress being driven by rapidly evolving preanalytical analytical procedures, integrated bioinformatics, machine learning algorithms. Yet, despite these spectacular advances, remains very challenging analyte due its immense heterogeneity fluctuation vivo. It increasingly recognized that high-fidelity reconstruction stored cfDNA, turn development fit roll-out, requires much deeper understanding both physico-chemical features biological, physiological, lifestyle, environmental factors modulate it. This daunting task, but significant upsides. In review we showed how expanded knowledge on biology faithful reverse-engineering samples promises (i) augment sensitivity specificity existing assays; (ii) expand repertoire disease-specific markers, thereby leading powerful (iii) reshape personal molecular medicine; (iv) have an unprecedented impact genetics research.

Language: Английский

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Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging

Psychoneuroendocrinology, Journal Year: 2023, Volume and Issue: 155, P. 106322 - 106322

Published: June 15, 2023

Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic results in load, dysregulated state predicts functional decline, accelerates aging, and increases mortality humans. The energetic cost cellular basis for damaging effects load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find glucocorticoid exposure energy expenditure ~60%, along with metabolic shift from glycolysis to mitochondrial oxidative phosphorylation (OxPhos). This stress-induced hypermetabolism is linked mtDNA instability, non-linearly affects age-related cytokines secretion, aging based on DNA methylation clocks, telomere shortening rate, reduced lifespan. Pharmacologically normalizing OxPhos activity while further increasing exacerbates accelerated phenotype, pointing total as potential driver dynamics. Together, our findings define bioenergetic multi-omic recalibrations stress adaptation, underscoring increased interrelated features load.

Language: Английский

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