Inhibition of Drp1- Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: March 4, 2024

Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, currently lacks specific effective treatment options. Mitochondrial dynamics dysfunction prominent feature in AKI, modulation of mitochondrial morphology may serve as potential therapeutic approach for AKI.

Language: Английский

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Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 327 - 327

Published: Jan. 31, 2025

Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in central nervous system (CNS) or peripheral (PNS). Examples neurodegenerative diseases include Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role cell signaling, immune response, metabolic regulation. For example, mitochondrial dysfunction is closely associated with onset progression variety diseases, including ND, cardiovascular diabetes, cancer. The energy metabolism, imbalance dynamics, abnormal mitophagy can lead homeostasis, which induce pathological reactions such as oxidative stress, apoptosis, inflammation, damage system, participate occurrence development degenerative AD, PD, ALS. In this paper, latest research progress subject detailed. mechanisms mitophagy-mediated ND are reviewed from perspectives β-amyloid (Aβ) accumulation, dopamine neuron damage, superoxide dismutase 1 (SOD1) mutation. Based on mechanism research, new ideas methods for treatment prevention proposed.

Language: Английский

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Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13033 - 13033

Published: Aug. 22, 2023

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death neurons, leading to range neurological symptoms. Despite heterogeneity these conditions, common denominator is implication mitochondrial dysfunction in their pathogenesis. Mitochondria play crucial role creating biomolecules, providing energy through adenosine triphosphate (ATP) generated oxidative phosphorylation (OXPHOS), producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented losing membrane potential, they contribute diseases. In this review, we explore how mitochondria fuse undergo fission, especially context NDs. We discuss genetic protein mutations linked impact dynamics. also look at key regulatory proteins fusion (MFN1, MFN2, OPA1) fission (DRP1 FIS1), including post-translational modifications. Furthermore, highlight potential drugs that can influence By unpacking complex processes, aim direct research towards treatments improve life quality for people with challenging conditions.

Language: Английский

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Imbalanced mitochondrial dynamics contributes to the pathogenesis of X-linked adrenoleukodystrophy

Brain, Journal Year: 2024, Volume and Issue: 147(6), P. 2069 - 2084

Published: Feb. 13, 2024

The peroxisomal disease adrenoleukodystrophy (X-ALD) is caused by loss of the transporter very-long-chain fatty acids (VLCFAs), ABCD1. An excess VLCFAs disrupts essential homeostatic functions crucial for axonal maintenance, including redox metabolism, glycolysis and mitochondrial respiration. As function morphology are intertwined, we set out to investigate role dynamics in X-ALD models. Using quantitative 3D transmission electron microscopy, revealed fragmentation corticospinal axons Abcd1- mice. In patient fibroblasts, an triggers through redox-dependent phosphorylation DRP1 (DRP1S616). blockade DRP1-driven fission peptide P110 effectively preserved morphology. Furthermore, mRNA inhibition not only prevented but also protected health a Caenorhabditis elegans model X-ALD, underscoring as potential therapeutic target. Elevated levels circulating cell-free mtDNA patients' CSF align this leukodystrophy with primary disorders. Our findings underscore intricate interplay between dysfunction, integrity shedding light on avenues intervention.

Language: Английский

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A Coupling‐Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 24, 2024

Abstract The strategy of in vivo self‐assembly has been developed for improved enrichment and long‐term retention anticancer drug tumor tissues. However, most self‐assemblies with non‐covalent bonding interactions are susceptible to complex physiological environments, leading weak stability loss biological function. Here, we develop a coupling‐induced assembly (CIA) generate covalently crosslinked nanofibers, which is applied situ constructing artificial shell on mitochondria. oxidation‐responsive peptide‐porphyrin conjugate P1 synthesized, self‐assemble into nanoparticles. Under the oxidative microenvironment mitochondria, coupling thiols causes formation dimers, further ordered stacked nanofibers. As result, constructed mitochondria efficiently through multivalent cooperative due increased binding sites. ultrasound (US) irradiation, porphyrin molecules produce large amount reactive oxygen species (ROS) that act adjacent mitochondrial membrane, exhibiting ~2‐fold higher antitumor activity than nanoparticles vitro vivo. Therefore, mitochondria‐targeted CIA provides novel perspective sonodynamic therapy (SDT) shows potential applications therapies.

Language: Английский

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Targeted downregulation of FIS1 in excitatory neurons within the spinal dorsal horn alleviates neuropathic pain through the mitigation of mitochondrial fragmentation

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

Published: Jan. 31, 2025

Background: Neuropathic pain has been shown to induce abnormal mitochondrial fission in neurons, yet the analgesic potential of inhibiting this process remains unclear. Our previous studies demonstrated that targeted regulation dynamin-related protein (DRP1) can alleviate neuropathic pain; however, downstream molecular signaling mechanisms remain be elucidated. Methods: To investigate role dynamics pain, we utilized C57BL/6J mice, GAD2-Cre and vGluT2-Cre mice. Mitochondrial network changes states were assessed using GAD2-MITO vGluT2-MITO transgenic mouse models combined with MiNA analysis. Pain thresholds expression levels various molecules spinal dorsal horn (SDH) evaluated through behavioral tests, immunofluorescence, Western blotting. morphology function conditions examined electron microscopy, membrane potential, reactive oxygen species, adenosine triphosphate assays. The effects antioxidant analgesics epigallocatechin gallate (EGCG) Cinnamic Acid on SDH during also investigated. Results: We observed networks both excitatory inhibitory neurons disrupted spared nerve injury as evidenced by models. Specifically, down-regulating FIS1 but not within elicited effects, experiments conducted Additionally, (EGCG), which effectively down-regulates SDH, concurrently inhibited SNI-induced pain. These findings suggest reducing fragmentation

Language: Английский

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Pyruvate kinase M2 modulates mitochondrial dynamics and EMT in alveolar epithelial cells during sepsis-associated pulmonary fibrosis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 19, 2025

Language: Английский

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The Essential Role of Mitochondrial Dynamics in Viral Infections

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1955 - 1955

Published: Feb. 24, 2025

Mitochondria are dynamic organelles that play crucial roles in energy production, metabolic balance, calcium homeostasis, apoptosis, and innate immunity, key determinants of cell fate. They also targets for viral invasion the body. Many proteins target mitochondria, controlling mitochondrial morphology, metabolism, immune response, thereby achieving evasion, promoting their proliferation, accelerating infection process. Mitochondrial quality control is to maintaining normal physiological functions homeostasis. Dysregulation dynamics closely related development many diseases. New constantly being discovered. Viruses change by targeting mitochondria achieve a persistent state infection. Currently, understanding during limited. Research on impact provides foundation investigating pathogenesis infections, disease process, identifying potential therapeutic targets. This review focuses connection between priority areas research virus-mediated insight into regulation viruses explores means mitochondrial-mediated treatment

Language: Английский

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Procyanidins inhibit alphacoronavirus infection by reducing interferon antagonism

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156549 - 156549

Published: Feb. 25, 2025

Language: Английский

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Hypertrophic Cardiomyopathy Through the Lens of Mitochondria

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 591 - 591

Published: Feb. 28, 2025

The mechanisms of pathogenesis hypertrophic cardiomyopathy are associated with mutations in the sarcomere genes cardiomyocytes and metabolic disorders cell, including mitochondrial dysfunction. Mitochondria characterized by presence their own DNA enzyme complexes involved oxidative reactions, which cause damage to protein structures membranes reactive oxygen species. Mitochondrial dysfunctions can also be encoding proteins lead a violation protective functions such as mitophagy, fusion, fission. Mutations myofibril negatively affect mitochondria through increased stress due an need for ATP. dysfunction is impaired ATP synthesis cardiac contractility, leading clinical manifestations cardiomyopathy. current review was designed characterize role based on published data; search publications analysis articles keywords “hypertrophic cardiomyopathy, mitochondria, dysfunction” PubMed Scopus databases up January 2025.

Language: Английский

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