Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

FEBS Letters, Год журнала: 2020, Номер 595(8), С. 1107 - 1131

Опубликована: Дек. 14, 2020

The majority of proteins localised to mitochondria are encoded by the nuclear genome, with approximately 1500 imported into mammalian mitochondria. Dysfunction in this fundamental cellular process is linked a variety pathologies including neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancer, demonstrating importance mitochondrial protein import machinery for function. Correct requires co-ordinated activity multimeric translocation sorting machineries located both outer inner membranes, directing destined compartment. This dynamic maintains homeostasis, its dysregulation significantly affects signalling pathways metabolism. review summarises current knowledge pathological consequences mutation components. In addition, we will discuss role our understanding Alzheimer's disease, Huntington's disease Parkinson's disease.

Язык: Английский

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Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

Frontiers in Cellular Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Сен. 24, 2021

Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body evidence suggests that neuroinflammation oxidative stress play negative role neurofunctional deficits. Red blood cells hemoglobin, immune cells, proinflammatory cytokines, peroxidases are directly or indirectly involved regulation central nervous system SAH. This review explores various cellular acellular components secondary inflammation SAH, aims to provide new ideas for clinical treatment improve prognosis

Язык: Английский

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Mitochondrial Transplantation as a Novel Therapeutic Strategy for Mitochondrial Diseases

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4793 - 4793

Опубликована: Апрель 30, 2021

Mitochondria are the major source of intercellular bioenergy in form ATP. They necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation metabolism apoptosis. Mitochondrial dysfunction has been observed variety diseases cardiovascular disease, aging, type 2 diabetes, cancer degenerative brain disease. In other words, interpretation mitochondrial signals potential to be applied a treatment various caused by disorders. recent years, transplantation increasingly topic interest an innovative strategy augmentation replacement mitochondria. this review, we focus on that associated with highlight studies related rescue tissue-specific We firmly believe is optimistic therapeutic approach finding potentially valuable diseases.

Язык: Английский

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Synapses: The Brain’s Energy-Demanding Sites

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3627 - 3627

Опубликована: Март 26, 2022

The brain is one of the most energy-consuming organs in mammalian body, and synaptic transmission major contributors. To meet these energetic requirements, primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. relevance two energy production pathways fulfilling at presynaptic terminals has been subject recent studies. In this review, we dissect balance phosphorylation to demands both resting stimulation conditions. Besides ATP output needs, mitochondria synapse are also important for calcium buffering regulation reactive oxygen species. These mitochondrial-associated pathways, once hampered, impact negatively on neuronal homeostasis activity. Therefore, as assume a critical role homeostasis, it becoming evident that population possesses distinct functional fingerprint compared other mitochondria. Ultimately, dysregulation bioenergetics glycolytic dysfunctions increasingly implicated neurodegenerative disorders, first hallmarks several diseases deficits, followed by degeneration.

Язык: Английский

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Mitochondrial Dysfunction: Pathophysiology and Mitochondria-Targeted Drug Delivery Approaches

Pharmaceutics, Год журнала: 2022, Номер 14(12), С. 2657 - 2657

Опубликована: Ноя. 30, 2022

Mitochondria are implicated in a wide range of functions apart from ATP generation, and, therefore, constitute one the most important organelles cell. Since healthy mitochondria essential for proper cellular functioning and survival, mitochondrial dysfunction may lead to various pathologies. considered novel promising therapeutic target diagnosis, treatment, prevention human diseases including metabolic disorders, cancer, neurodegenerative diseases. For mitochondria-targeted therapy, there is need develop an effective drug delivery approach, owing special bilayer structure through which molecules undergo multiple difficulties reaching core. In recent years, nanoformulations have been designed such as polymeric nanoparticles, liposomes, inorganic nanoparticles conjugate with mitochondriotropic moieties mitochondria-penetrating peptides (MPPs), triphenylphosphonium (TPP), dequalinium (DQA), protein import machinery overcoming barriers involved targeting mitochondria. The current approaches used provided ways overcome challenges associated targeted-drug delivery. Herein, we review research past years scenario that has identified major contributor pathophysiology Furthermore, discuss advancements strategies pathologies dysfunction.

Язык: Английский

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The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Cells, Год журнала: 2022, Номер 11(13), С. 2049 - 2049

Опубликована: Июнь 28, 2022

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and highly fatal neurodegenerative disease. Although the pathogenesis of ALS remains unclear, increasing evidence suggests that key contributing factor mitochondrial dysfunction. Mitochondria are organelles in eukaryotic cells responsible for bioenergy production, cellular metabolism, signal transduction, calcium homeostasis, immune responses stability their function plays crucial role neurons. A single disorder or defect can lead to pathological changes cells, such as an impaired buffer period, excessive generation free radicals, increased membrane permeability, oxidative stress (OS). Recent research has also shown these dysfunctions associated with believed be commonly involved This article reviews latest on dysfunction its impact progression ALS, specific attention potential novel therapeutic strategies targeting

Язык: Английский

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Mitochondrial dysfunctions in neurodegenerative diseases: role in disease pathogenesis, strategies for analysis and therapeutic prospects

Neural Regeneration Research, Год журнала: 2021, Номер 17(4), С. 754 - 754

Опубликована: Авг. 29, 2021

Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes, mitochondria are required for multiple pivotal processes include production biological energy, biosynthesis reactive oxygen species, control calcium homeostasis, and triggering death. The disruption anyone these has been shown to impact strongly function all cells, but especially neurons. In this review, we discuss role impairment development neurodegenerative diseases Amyotrophic Lateral Sclerosis, Parkinson's disease Alzheimer's disease. We highlight how revolves around underlie mitochondria's life cycle: fusion, fission, species energy failure. Both genetic sporadic forms unavoidably accompanied often caused by dysfunction one or more key mitochondrial processes. Therefore, order get depth insights into their health status diseases, need focus innovative strategies aimed at characterizing various Current techniques Mitostress, Mitotracker, transmission electron microscopy, oxidative stress assays along expression measurement proteins maintain health. will also a panel approaches mitigating dysfunction. These canonical drugs, natural compounds, supplements, lifestyle interventions as transplantation gene therapy. conclusion, because fundamental necessary virtually functions severely impaired it is critical develop novel methods measure state, therapeutic improving

Язык: Английский

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Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes

The Journal of Cell Biology, Год журнала: 2022, Номер 222(1)

Опубликована: Ноя. 16, 2022

Astrocytes, often considered as secondary responders to neurodegeneration, are emerging primary drivers of brain disease. Here we show that mitochondrial DNA depletion in astrocytes affects their cilium, the signaling organelle a cell. The progressive oxidative phosphorylation deficiency induces FOXJ1 and RFX transcription factors, known master regulators motile ciliogenesis. Consequently, robust gene expression program involving cilia components multiciliated cell differentiation factors induced. While affected still retain single these organelles elongate become remarkably distorted. data suggest chronic activation integrated stress response (ISRmt) drives anabolic metabolism promotes ciliary elongation. Collectively, our evidence indicates an active axis mitochondria exists is part ISRmt astrocytes. We propose metabolic ciliopathy novel pathomechanism for mitochondria-related neurodegenerative diseases.

Язык: Английский

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Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan-Kynurenine Metabolic System

Опубликована: Июль 8, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently growing preclinical studies that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among other. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation have linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This narrative review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Язык: Английский

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Protective Effects of Pioglitazone on Cognitive Impairment and the Underlying Mechanisms: A Review of Literature

Drug Design Development and Therapy, Год журнала: 2022, Номер Volume 16, С. 2919 - 2931

Опубликована: Авг. 1, 2022

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is known to have anti-inflammatory and anti-oxidant effects on the brain, its clinical potential in treatment of cognitive impairment diseases such as Alzheimer's disease (AD) Parkinson (PD) currently being explored. This review focused reported beneficial pioglitazone dysfunction summarized associated mechanisms with pioglitazone-induced improvement dysfunction. Our relevant literature indicated that there conclusive evidence effect improving via agonistic PPAR-γ. Further, several action been reported, these include enhanced NF-kB p38 activity; regulation pro-inflammatory cytokines IL-1, IL-6, TNF-α; inhibition Aβ production; alterations levels mitochondrial proteins mitoNEET; protein kinases CDK5 JNK; ROS MDA antioxidant TRX1 PON2; increased expression thyroid hormone receptors. Despite promising findings, also cardiovascular risks, weight gain edema, which subsequently increase risk mortality. it has documented may be unable cross blood-brain barrier when administered certain forms, can cause cell death at high concentrations. Therefore, further research required explore acute chronic memory function order determine applicability disorders. Nonetheless, current does demonstrate promotes PPAR receptors ameliorating inflammation, oxidative stress, amyloidogenesis, hypothyroidism, enhancing neurogenesis, synaptic plasticity, function. warrant investigation establish disorders, PD AD, neuronal conditions diabetes.

Язык: Английский

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