Function and regulation of the divisome for mitochondrial fission

Nature, Год журнала: 2021, Номер 590(7844), С. 57 - 66

Опубликована: Фев. 3, 2021

Язык: Английский

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Quality control of the mitochondrion

Developmental Cell, Год журнала: 2021, Номер 56(7), С. 881 - 905

Опубликована: Март 7, 2021

Язык: Английский

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Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction

Nature Metabolism, Год журнала: 2023, Номер 5(4), С. 546 - 562

Опубликована: Апрель 26, 2023

Язык: Английский

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Phosphoglycerate mutase 5 exacerbates cardiac ischemia-reperfusion injury through disrupting mitochondrial quality control

Redox Biology, Год журнала: 2020, Номер 38, С. 101777 - 101777

Опубликована: Ноя. 1, 2020

The death of cardiomyocytes either through apoptosis or necroptosis is the pathological feature cardiac ischemia-reperfusion (I/R) injury. Phosphoglycerate mutase 5 (PGAM5), a mitochondrially-localized serine/threonine-protein phosphatase, functions as novel inducer necroptosis. However, intense debate exists regarding effect PGAM5 on I/R-related cardiomyocyte death. Using cardiac-specific knockout (PGAM5CKO) mice, we comprehensively investigated precise contribution and molecular mechanism in Our data showed that both transcription expression were upregulated reperfused myocardium. Genetic ablation suppressed I/R-mediated but failed to prevent activation, result went along with improved heart function decreased inflammation response. Regardless status, mitophagy-related cell was not apparent following I/R. Under physiological conditions, overexpression primary sufficient induce rather than apoptosis. At sub-cellular levels, deficiency increased mitochondrial DNA copy number transcript normalized respiration, repressed ROS production, prevented abnormal mPTP opening upon Molecular investigation demonstrated deletion interrupted DrpS637 dephosphorylation abolish I/R-induce Drp1S616 phosphorylation, resulting partial inhibition fission. In addition, declining Mfn2 OPA1 levels restored PGAM5CKO Nevertheless, depletion did rescue mitophagy I/R conclusion, our results provide an insight into specific role working driving imposing quality control

Язык: Английский

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Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 8

Опубликована: Янв. 5, 2021

The underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This supported by already large rapidly growing body evidence showing that the role (dys)function central multifaceted. However, there are clear gaps in knowledge, including dilemma explaining why inherited mitochondriopathies do not usually present with parkinsonian symptoms. Many aspects function potential therapeutic targets, reactive oxygen species production, mitophagy, biogenesis, dynamics trafficking, metal ion homeostasis, sirtuins, endoplasmic reticulum links mitochondria. Potential strategies may also incorporate exercise, microRNAs, transplantation, stem cell therapies, photobiomodulation. Despite multiple studies adopting numerous treatment strategies, clinical trials to date have generally failed show benefit. To overcome this hurdle, more accurate biomarkers required detect subtle beneficial effects. Furthermore, selecting study participants early course, studying them for suitable durations, stratifying according genetic neuroimaging findings increase likelihood successful trials. Moreover, treatments involving combined approaches will likely better address complexity disease. Therefore, right patients, at time, using targeted combination treatments, offer best chance development effective novel therapy targeting

Язык: Английский

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Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy

Redox Biology, Год журнала: 2022, Номер 52, С. 102304 - 102304

Опубликована: Апрель 6, 2022

As essential regulators of mitochondrial quality control, dynamics and mitophagy play key roles in maintenance metabolic health cellular homeostasis. Here we show that knockdown the membrane-inserted scaffolding structural protein caveolin-1 (Cav-1) expression tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered morphology, increased matrix mixing, fusion fission well MDA-MB-231 triple negative breast cancer cells. Further, found interaction with fusion/fission machinery Mitofusin 2 (Mfn2) Dynamin related 1 (Drp1) was enhanced by Y14D indicating Y14 phosphorylation prevented Mfn2 Drp1 translocation mitochondria. Moreover, limiting recruitment diminished formation PINK1/Mfn2/Parkin complex required for initiation resulting accumulation damaged mitochondria ROS (mtROS). Thus, these studies indicate phospho-Cav-1 may be an important switch mechanism cell survival which could lead novel strategies complementing therapies.

Язык: Английский

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Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Язык: Английский

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Quantifying organellar ultrastructure in cryo-electron tomography using a surface morphometrics pipeline

The Journal of Cell Biology, Год журнала: 2023, Номер 222(4)

Опубликована: Фев. 14, 2023

Cellular cryo-electron tomography (cryo-ET) enables three-dimensional reconstructions of organelles in their native cellular environment at subnanometer resolution. However, quantifying ultrastructural features pleomorphic three dimensions is challenging, as defining the significance observed changes induced by specific perturbations. To address this challenge, we established a semiautomated workflow to segment organellar membranes and reconstruct underlying surface geometry cryo-ET. complement workflow, developed an open-source suite quantifications, integrated into single pipeline called morphometrics pipeline. This rapid modeling complex membrane structures allows detailed mapping inter- intramembrane spacing, curvedness, orientation onto reconstructed meshes, highlighting subtle that are challenging detect allowing for statistical comparison across many organelles. demonstrate advantages approach, combine cryo-ET with cryo-fluorescence microscopy correlate bulk mitochondrial network morphology (i.e., elongated versus fragmented) ultrastructure individual mitochondria presence absence endoplasmic reticulum (ER) stress. Using our pipeline, ER stress promotes adaptive remodeling including spacing between inner outer membranes, local curvedness membrane, cristae. We show differences morphologies, suggesting these two events coupled. Our offers opportunities on single-cell level using cryo-ET, opening new define diverse types

Язык: Английский

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Mitochondrial quality control in human health and disease

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Май 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Язык: Английский

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Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration

Advanced Science, Год журнала: 2021, Номер 8(20)

Опубликована: Авг. 16, 2021

As a chronic metabolic disease, diabetes mellitus (DM) creates hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because mitochondrial dysfunction in hyperglycemia. To address the daunting issue, authors innovatively devised developed mitochondria-targeted orthopedic implants consisted nutrient element coatings polyetheretherketone (PEEK). Dual elements, modality ZnO Sr(OH)2 , are assembled onto sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate synergistic liberation Zn2+ Sr2+ from coating massacres pathogenic bacteria dramatically facilitates cyto-activity osteoblasts upon niche. Intriguingly, Zn&Sr-SPEEK demonstrated to have robust ability recuperate hyperglycemia-induced dynamic disequilibrium by means Dynamin-related protein 1 (Drp1) gene down-regulation, membrane potential (MMP) resurgence, reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 8 weeks further confirm that substantially augment bone remodeling osseointegration. Altogether, this study not only reveals importance modulation on dynamics contributes formation osseointegration, but also provides novel implant for patients with capability.

Язык: Английский

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