The interplay between mitochondrial dynamics and autophagy: From a key homeostatic mechanism to a driver of pathology

Seminars in Cell and Developmental Biology, Год журнала: 2024, Номер 161-162, С. 1 - 19

Опубликована: Март 1, 2024

The complex relationship between mitochondrial dynamics and autophagy illustrates how two cellular housekeeping processes are intimately linked, illuminating fundamental principles of homeostasis shedding light on disparate pathological conditions including several neurodegenerative disorders. Here we review the basic tenets i.e., concerted balance fusion fission organelle, its interplay with macroautophagy selective autophagy, also dubbed mitophagy, in maintenance quality control ultimately cell viability. We illustrate altered reverberate vice versa. Finally, these key participates pathogenesis human disorders affecting multiple organs systems.

Язык: Английский

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Extracellular vesicles, RNA sequencing, and bioinformatic analyses: Challenges, solutions, and recommendations

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(12)

Опубликована: Дек. 1, 2024

Abstract Extracellular vesicles (EVs) are heterogeneous entities secreted by cells into their microenvironment and systemic circulation. Circulating EVs carry functional small RNAs other molecular footprints from cell of origin, thus have evident applications in liquid biopsy, therapeutics, intercellular communication. Yet, the complete transcriptomic landscape is poorly characterized due to critical limitations including variable protocols used for EV‐RNA extraction, quality control, cDNA library preparation, sequencing technologies, bioinformatic analyses. Consequently, there a gap knowledge need standardized approach delineating EV‐RNAs. Here, we address these gaps describing following points (1) focusing on large canopy particles (EVPs), which includes, but not limited – exosomes EVs, lipoproteins, exomeres/supermeres, mitochondrial‐derived vesicles, RNA binding proteins, cell‐free DNA/RNA/proteins; (2) examining potential roles biogenesis EVPs; (3) discussing various methods technologies uncovering cargoes (4) presenting comprehensive list subtypes reported (5) different databases resources specific species; (6) reviewing established bioinformatics pipelines novel strategies reproducible EV transcriptomics analyses; (7) emphasizing significant gold standard identifying EV‐RNAs across studies; (8) finally, highlight current challenges, discuss possible solutions, present recommendations robust analyses EVP‐associated RNAs. Overall, seek provide clarity landscape, EVP‐RNAs. Detailed portrayal state EVP will lead better understanding how cargo EVPs can be modern targeted diagnostics therapeutics. For inclusion discussed this article, use terms large/small non‐vesicular extracellular (NVEPs), EPs as defined MISEV guidelines International Society Vesicles (ISEV).

Язык: Английский

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Mitochondrial derived vesicles‐ Quo Vadis?

FEBS Journal, Год журнала: 2024, Номер 291(21), С. 4660 - 4669

Опубликована: Фев. 27, 2024

Mitochondria are dynamic, intracellular organelles with a separate genome originating from prokaryotes. They perform numerous functions essential for cellular metabolism and energy production. Mitochondrial‐derived vesicles (MDVs) single or double membrane‐enclosed vesicles, formed released the mitochondrial sub‐compartments into cytosol, in response to various triggers. MDVs interact other such as lysosomes peroxisomes may be incorporated excreted via extracellular (EVs). selectively incorporate diverse protein lipid cargoes involved quality control, immunomodulation, complementation, compartmentalization transport. This review aims provide summary of current knowledge biogenesis, release, cargoes, roles.

Язык: Английский

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The functional regulation between extracellular vesicles and the DNA damage responses

Mutation Research/Reviews in Mutation Research, Год журнала: 2025, Номер 795, С. 108532 - 108532

Опубликована: Янв. 1, 2025

Язык: Английский

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Mitochondrial Dysfunction in Neurodegenerative Diseases

Cells, Год журнала: 2025, Номер 14(4), С. 276 - 276

Опубликована: Фев. 13, 2025

Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's Huntington's and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical pathological features, exhibit shared pathways leading to neuronal damage, all which are closely associated with mitochondrial dysfunction. The high metabolic requirements neurons make even minor deficiencies highly impactful, driving oxidative stress, energy deficits, aberrant protein processing. Growing evidence from genetic, biochemical, cellular investigations associates impaired electron transport chain activity disrupted quality-control mechanisms, such as mitophagy, the initial phases disease progression. Furthermore, overproduction reactive oxygen species persistent neuroinflammation can establish feedforward cycles that exacerbate deterioration. Recent research has increasingly focused on interventions aimed at enhancing resilience-through antioxidants, small molecules modulate balance fusion fission, or gene-based therapeutic strategies. Concurrently, initiatives identify dependable biomarkers seek detect changes prior manifestation overt symptoms. By integrating current body knowledge, this review emphasizes critical role preserving homeostasis viable approach. It also addresses complexities translating these findings into practice underscores potential innovative strategies designed delay potentially halt processes.

Язык: Английский

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Mitochondria: An overview of their origin, genome, architecture, and dynamics

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167803 - 167803

Опубликована: Март 1, 2025

Язык: Английский

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Utilizing Extracellular Vesicles for Eliminating ‘Unwanted Molecules’: Harnessing Nature’s Structures in Modern Therapeutic Strategies

Molecules, Год журнала: 2024, Номер 29(5), С. 948 - 948

Опубликована: Фев. 21, 2024

Extracellular vesicles (EVs) are small phospholipid bilayer-bond structures released by diverse cell types into the extracellular environment, maintaining homeostasis of balancing cellular stress. This article provides a comprehensive overview vesicles, their heterogeneity, and diversified roles in processes, emphasizing importance elimination unwanted molecules. They play role regulating oxidative stress, particularly discarding oxidized toxic Furthermore, endoplasmic reticulum stress induces release EVs, contributing to distinct results, including autophagy or ER transmission following cells. stress-induced is part unfolded protein response (UPR) protects cells from stress-related apoptosis. Mitochondrial-derived (MDVs) also homeostasis, as they carry damaged mitochondrial components, thereby preventing inflammation. Moreover, EVs partake aging-related therefore can potentially crucial anti-aging therapies, treatment age-related diseases such Alzheimer’s disease cardiovascular conditions. Overall, purpose this provide better understanding significant mediators both physiological pathological shed light on potential for therapeutic interventions targeting EV-mediated pathways various conditions, with an emphasis diseases.

Язык: Английский

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Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders

Cell & Bioscience, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 8, 2024

Abstract Chronic inflammatory musculoskeletal disorders characterized by prolonged muscle inflammation, resulting in enduring pain and diminished functionality, pose significant challenges for the patients. Emerging scientific evidence points to mitochondrial malfunction as a pivotal factor contributing these ailments. Mitochondria play critical role powering skeletal activity, but context of persistent disruptions their quantity, configuration, performance have been well-documented. Various disturbances, encompassing alterations dynamics (such fission fusion), calcium regulation, oxidative stress, biogenesis, process mitophagy, are believed central progression disorders. Additionally, unfolded protein responses accumulation fatty acids within cells may adversely affect internal milieu, impairing equilibrium functioning. The structural discrepancies between different subsets namely, intramyofibrillar subsarcolemmal mitochondria likely impact metabolic capabilities susceptibility influences. release signals from damaged is known incite responses. Intriguingly, migrasomes extracellular vesicles serve vehicles intercellular transfer mitochondria, aiding removal impaired regulation inflammation. Viral infections implicated inducing stress on mitochondria. Prolonged dysfunction vital organelles sustains harm, irregularities, heightened cytokine release, impeding body’s ability repair tissues. This review provides comprehensive analysis advancements understanding changes intracellular environment, architecture distribution, dynamics, autophagy, cytokines associated with vesicular structures, membranes chronic Strategies targeting key elements regulating quality exhibit promise restoration function, alleviation enhancement overall outcomes. Graphical

Язык: Английский

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From exosomes to mitochondria and myocardial infarction: molecular insight and therapeutic challenge

Pharmacological Research, Год журнала: 2024, Номер 209, С. 107468 - 107468

Опубликована: Окт. 18, 2024

Myocardial infarction (MI) remains a leading cause of mortality worldwide. Despite patients with MI benefit from timely reperfusion therapies, the rates and morbidity remain substantial, suggesting an enduring need for development new approaches. Molecular mechanisms underlying myocardial ischemic injury are associated both cardiomyocytes non-cardiomyocytes. Exosomes nano-sized extracellular vesicles released by almost all eukaryotic cells. They facilitate communication between various cells transferring information via their cargo altering different biological activities in recipient Studies have created great prospects therapeutic applications exosomes MI, as demonstrated through beneficial effect on heart function reducing ventricular remodeling association fibrosis, angiogenesis, apoptosis, inflammation. Of note, is primarily due to restricted blood flow, oxygen availability, causing inefficient utilization energy substrates. However, impact cardiac metabolism has not been adequately investigated. Although engineered targeted delivery enhance clinical efficacy, challenges must be overcome utilize them reliably clinic. In this review, we summarize research progress focus known unknown regarding role non-cardiomyocytes; well potential avenues exosome-mitochondrial regulation challenges. We aim help identify more efficient molecular targets that may promote application exosomes.

Язык: Английский

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Exosome: an overview on enhanced biogenesis by small molecules

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 25, 2025

Язык: Английский

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