Mitochondrion最新文献_第6页

Targeting mitochondrial quality control for myocardial ischemia-reperfusion injury 心肌缺血再灌注损伤的线粒体质量控制

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-05-24 DOI: 10.1016/j.mito.2025.102046

Yuxuan He , Sixu Ren , Chenglin Liu , Xiufen Zheng , Cuilin Zhu

Cardiovascular disease (CVD) remains the leading global cause of mortality. Acute myocardial infarction (AMI) refers to acute myocardial ischemia resulting from thrombosis secondary to coronary atherosclerosis, which poses a major threat to human health. Clinically, timely revascularization (reperfusion) represents the basis of clinical treatment for AMI. However, secondary myocardial ischemia–reperfusion injury (MIRI) caused by reperfusion often exacerbates damage, representing a major challenge in clinical practice. Mitochondria represent essential organelles for maintaining cardiac function and cellular bioenergetics in MIRI. In recent years, the role of mitochondrial quality control (MQC) in maintaining cell homeostasis and mediating MIRI has been extensively studied. This review provides a concise overview of MQC mechanisms at the molecular, organelle, and cellular levels and their possible complex regulatory network in MIRI. In addition, potential treatment strategies targeting MQC to mitigate MIRI are summarized, highlighting the gap between current preclinical research and clinical transformation. Overall, this review provides theoretical guidance for further research and clinical translational studies.

心血管疾病（CVD）仍然是全球主要的死亡原因。急性心肌梗死（Acute myocardial infarction， AMI）是指冠状动脉粥样硬化继发的血栓形成导致的急性心肌缺血，对人类健康构成重大威胁。在临床上，及时的再灌注是AMI临床治疗的基础。然而，再灌注引起的继发性心肌缺血-再灌注损伤（MIRI）往往会加剧损伤，这是临床实践中的一个主要挑战。线粒体是维持心脏功能和细胞生物能量的重要细胞器。近年来，线粒体质量控制（MQC）在维持细胞稳态和介导MIRI中的作用得到了广泛的研究。本文综述了MIRI在分子、细胞器和细胞水平上的MQC机制及其可能的复杂调控网络。此外，总结了针对MQC缓解MIRI的潜在治疗策略，强调了目前临床前研究与临床转化之间的差距。综上所述，本文为进一步的研究和临床转化研究提供了理论指导。

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引用次数: 0

Miro1- a key player in β-cell function and mitochondrial dynamics under diabetes mellitus Miro1--糖尿病情况下β细胞功能和线粒体动力学的关键参与者

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-04-07 DOI: 10.1016/j.mito.2025.102039

Srikanth Kavyashree, Kannan Harithpriya, Kunka Mohanram Ramkumar

Mitochondrial health is crucial for the survival and function of β-cells, preserving glucose homeostasis and effective insulin production. Miro1, a mitochondrial Rho GTPase1 protein, plays an essential role in maintaining the quality of mitochondria by regulating calcium homeostasis and mitophagy. In this review, we aim to explore the dysfunction of Miro1 in type 2 diabetes mellitus (T2DM) and its contribution to impaired Ca²⁺ signaling, which increases oxidative stress in β-cells. This dysfunction is the hallmark of T2DM pathogenesis, leading to insufficient insulin production and poor glycemic control. Additionally, we discuss the role of Miro1 in modulating insulin secretion and inflammation, highlighting its effect on modulating key signaling cascades in β-cells. Altogether, enhancing Miro1 function and activity could alleviate mitochondrial dysfunction, reducing oxidative stress-mediated damage, and improving pancreatic β-cell survival. Targeting Miro1 with small molecules or gene-editing approaches could provide effective strategies for restoring cell function and insulin secretion in diabetic individuals. Exploring the deeper knowledge of Miro1 functions and interactions could lead to novel therapeutic advances in T2DM management.

线粒体的健康对β细胞的存活和功能、保持葡萄糖稳态和有效分泌胰岛素至关重要。线粒体 Rho GTPase1 蛋白 Miro1 通过调节钙平衡和有丝分裂，在维持线粒体质量方面发挥着重要作用。在这篇综述中，我们旨在探讨 Miro1 在 2 型糖尿病（T2DM）中的功能障碍及其对 Ca2+ 信号转导受损的贡献，而 Ca2+ 信号转导受损会增加 β 细胞的氧化应激。这种功能障碍是 T2DM 发病机制的标志，会导致胰岛素分泌不足和血糖控制不良。此外，我们还讨论了 Miro1 在调节胰岛素分泌和炎症中的作用，强调了它对调节 β 细胞中关键信号级联的影响。总之，增强 Miro1 的功能和活性可以缓解线粒体功能障碍，减少氧化应激介导的损伤，提高胰岛β细胞的存活率。用小分子或基因编辑方法靶向 Miro1 可为恢复糖尿病患者的细胞功能和胰岛素分泌提供有效的策略。深入了解 Miro1 的功能和相互作用可为治疗 T2DM 带来新的进展。

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引用次数: 0

Auditory neuropathy spectrum disorder and related auditory features in patients with hearing loss associated with the MT-TS1 m.7471dup variant MT-TS1 m.7471dup变异相关听力损失患者的听神经病变谱障碍和相关听觉特征

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-05-20 DOI: 10.1016/j.mito.2025.102056

Shujiro Minami , Amina Kida , Satomi Inoue , Haruka Murakami , Noriko Morita , Akira Takagi , Takeshi Usui , Tomoko Sugiuchi , Kazuki Yamazawa , Kiyomitsu Nara , Hideki Mutai , Tatsuo Matsunaga

The m.7471dup variant of mitochondrial-tRNA Ser (UCN) (MT-TS1) is associated with sensorineural hearing loss (SNHL), neurological abnormalities, or both. Phenotypic variations in SNHL associated with the m.7471dup variant were the focus of our investigation. Five Japanese families carrying the variant were subjected to comprehensive genetic and clinical evaluations and audiometric testing. Notably, two families presented with auditory neuropathy spectrum disorder (ANSD), and two other families presented with auditory brainstem response thresholds much higher than those expected from the pure-tone audiometry results, which is analogous to ANSD. This is the first study to demonstrate that the m.7471dup variant can be associated with ANSD or similar characteristics. The penetrance of the m.7471dup variant was 71.4 % overall, with 100 % penetrance in cases with homoplasmy and 42.9 % penetrance in cases with heteroplasmy. Disease onset was congenital or early onset (≤ 6 years) in 80 % of the patients. The hearing levels ranged from normal to profound, and four subjects presented with neurological or psychiatric abnormalities. About 80 % of subjects who had newborn hearing screening passed the screening, suggesting late-onset or progressive hearing loss. These findings underscore the importance of rigorous follow-up evaluations, genetic counseling, and evaluation of educational environment considerations for patients carrying the m.7471dup variant.

线粒体- trna Ser (UCN) （MT-TS1）的m.7471dup变异与感音神经性听力损失（SNHL）、神经异常或两者兼而有之有关。与m.7471dup变异相关的SNHL表型变异是我们研究的重点。携带该变异的5个日本家庭接受了全面的遗传和临床评估以及听力测试。值得注意的是，两个家庭表现为听觉神经病变谱系障碍（ANSD），另外两个家庭表现为听觉脑干反应阈值远高于纯音听力学结果的预期值，这与ANSD类似。这是第一个证明m.7471dup变异可能与ANSD或类似特征相关的研究。m.7471dup变异的总体外显率为71.4 %，同质外显率为100 %，异质外显率为42.9% %。80% %的患者为先天性或早发性（≤6年）。听力水平从正常到深度不等，四名受试者表现出神经或精神异常。约80% %新生儿听力筛查的受试者通过筛查，提示迟发性或进行性听力损失。这些发现强调了对携带m.7471dup变异的患者进行严格的随访评估、遗传咨询和教育环境评估的重要性。

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引用次数: 0

Urolithin-A supplementation alleviates sepsis-induced acute lung injury by reducing mitochondrial dysfunction and modulating macrophage polarization 补充尿石素- a可通过降低线粒体功能障碍和调节巨噬细胞极化来减轻败血症引起的急性肺损伤

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-05-04 DOI: 10.1016/j.mito.2025.102047

Mohd Mohsin , Almaz Zaki , Gulnaz Tabassum , Salman Khan , Shakir Ali , Tanveer Ahmad , Mansoor Ali Syed

Sepsis is a severe and life-threatening condition marked by excessive inflammation, mitochondrial dysfunction, and epithelial barrier disruption, often leading to Acute Lung Injury (ALI). Mitophagy, a cellular mechanism that removes damaged mitochondria, plays a vital role in maintaining mitochondrial health during sepsis. In this study, we investigated the protective effects of Urolithin-A against ALI and sepsis. In LPS-stimulated RAW264.7 macrophages, Urolithin-A significantly reduced mitochondrial dysfunction, Reactive Oxygen Species (ROS), Nitric Oxide (NO) production, and apoptosis. Additionally, it enhanced mitophagy by upregulating PINK1, Parkin, and LC3-II, which helped preserve mitochondrial function.

In vivo, Urolithin-A treatment in mouse models of ALI and sepsis reduced lung injury and inflammation, as shown by improved ALI scores, decreased wet/dry lung weight ratios, and lower levels of inflammatory markers such as iNOS, IL-1β, and MPO. Urolithin-A also improved epithelial barrier integrity and upregulated anti-apoptotic markers, demonstrating its ability to alleviate sepsis-induced lung damage. These findings suggest that Urolithin-A holds significant promise as a therapeutic agent for managing inflammatory lung conditions associated with sepsis.

脓毒症是一种严重的危及生命的疾病，其特征是过度炎症、线粒体功能障碍和上皮屏障破坏，通常导致急性肺损伤（ALI）。线粒体自噬是一种清除受损线粒体的细胞机制，在脓毒症期间维持线粒体健康方面起着至关重要的作用。在这项研究中，我们研究了尿石素- a对ALI和脓毒症的保护作用。在lps刺激的RAW264.7巨噬细胞中，尿石素- a显著降低线粒体功能障碍、活性氧（ROS）、一氧化氮（NO）的产生和细胞凋亡。此外，它通过上调PINK1、Parkin和LC3-II来增强线粒体自噬，这有助于保持线粒体功能。在体内，尿石素- a治疗ALI和脓毒症小鼠模型可减轻肺损伤和炎症，如ALI评分提高、肺干/湿重比降低、炎症标志物如iNOS、IL-1β和MPO水平降低所示。尿石素-a还能改善上皮屏障的完整性，上调抗凋亡标志物，证明其能够减轻败血症诱导的肺损伤。这些发现表明尿石素- a作为治疗与败血症相关的炎症性肺部疾病的治疗药物具有重要的前景。

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引用次数: 0

Chlordecone (kepone) induces mitochondrial dysfunction in human cardiac tissue 十氯酮（酮）诱导人心脏组织线粒体功能障碍。

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.mito.2025.102058

Alexia FUNDERE , Marie-Daniela DUBOIS , Magalie VATIN INAMO , Fatima RADOUANI , Prisca JALTA , Dabor RESIERE , Remi NEVIERE

Chlordecone exposure in humans has been associated with increased incidence of prostate cancer, impaired fertility, and fetal/perinatal abnormalities while experiment rodent studies suggest that chlordecone can inhibit magnesium-ATPase, little is known about its mitochondrial toxicity in humans. Our objective was to test whether chlordecone would induce mitochondrial dysfunction in human cardiac cells in ex vivo heart preparations. Biopsies of human atrial tissue were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing programmed cardiac surgery for coronary artery bypass. Cardiac preparations were incubated with vehicle or chlordecone (5 nM and 50 nM) for 24 hr followed by mitochondrial high-resolution oxygraphy studies. Compared with vehicle, chlordecone cardiac exposure at the concentrations of 5 nM and 50 nM impaired mitochondrial respiratory rates. Chlordecone concentrations of 5 nM and 50 nM similarly increased state 2 respiration rate and maximal respiration capacity with no change of state 3 (ADP) respiration rate, which suggests the uncoupling of between mitochondrial oxidative phosphorylation and electron transport through the respiratory chain complexes. In conclusion, our study suggests that chlordecone at clinically relevant concentration impairs mitochondrial function leading to uncoupling, which may induce abnormal cardiac cell responses, including aberrant calcium handling and oxidative stress.

十氯酮暴露于人体内与前列腺癌发病率增加、生育能力受损和胎儿/围产期异常有关，而啮齿类动物实验研究表明，十氯酮可以抑制镁三磷酸腺苷酶，但对其在人体内的线粒体毒性知之甚少。我们的目的是测试十氯酮是否会在离体心脏制剂中诱导人心肌细胞线粒体功能障碍。在体外循环插管期间，从接受程序性心脏手术进行冠状动脉搭桥的患者中获得人类心房组织活检。心脏制剂与载体或十氯酮（5 nM和50 nM）孵育24 小时，然后进行线粒体高分辨率氧成像研究。与对照组相比，浓度为5 nM和50 nM的十氯酮心脏暴露使线粒体呼吸速率受损。浓度为5 nM和50 nM的十氯酮同样增加了状态2呼吸速率和最大呼吸量，而状态3 （ADP）呼吸速率没有变化，这表明线粒体氧化磷酸化和电子通过呼吸链复合物传递之间的解耦合。总之，我们的研究表明，临床相关浓度的十氯酮会损害线粒体功能，导致解偶联，从而可能引起异常的心肌细胞反应，包括异常的钙处理和氧化应激。

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引用次数: 0

Mitochondrial health, prenatal distress, and gestational age: investigation of cf-mtDNA and GDF15 in two pregnancy studies from the USA and Turkey 线粒体健康、产前窘迫和胎龄：美国和土耳其两项妊娠研究中cf-mtDNA和GDF15的调查

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-06-03 DOI: 10.1016/j.mito.2025.102057

Qiuhan Huang , David Shire , Fiona Hollis , Sameera Abuaish , Martin Picard , Catherine Monk , Elif Aysimi Duman , Caroline Trumpff

Background

Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for energy production and stress adaptation, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey.

Methods

We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N = 187, USA) and BABIP (N = 198, Turkey). Data were collected at multiple timepoints during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4–14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests.

Results

Plasma cf-mtDNA levels did not significantly vary across pregnancy, while plasma GDF15 levels increased from early to late pregnancy and decreased postpartum. Late 2nd trimester plasma GDF15 was negatively correlated with pre-pregnancy BMI (p = 0.035) and gestational age (p = 0.0048) at birth. Early 2nd trimester maternal distress was associated with lower cf-mtDNA (all p-values < 0.05) and a trend for lower GDF15. Higher pre-pregnancy BMI and late-pregnancy maternal distress were linked to smaller postpartum GDF15 declines in EPI (all p-values < 0.05).

Conclusions

This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, linking these mitochondrial markers to maternal distress and pregnancy outcomes.

背景：妊娠结局受到母亲痛苦的影响，但这些影响背后的途径尚不清楚。线粒体对能量产生和压力适应至关重要，可能将社会心理压力与其生物效应联系起来，特别是在能量需求显著增加的怀孕期间。本研究在美国和土耳其的两项纵向研究中探讨了两种线粒体标记物——循环无细胞线粒体DNA （cf-mtDNA）和生长分化因子-15 （GDF15）——作为潜在的线粒体健康指标，将母亲的痛苦与妊娠结局联系起来。方法：我们分析了两项妊娠研究中妇女的生物学、人口学和心理数据：EPI （N = 187，美国）和BABIP （N = 198，土耳其）。在围产期的多个时间点收集数据，包括妊娠晚期和妊娠晚期，EPI还包括妊娠早期和产后4-14个月 的额外数据。产前母亲的心理困扰被测量为感知压力、焦虑和抑郁症状。分别采用qPCR和ELISA检测血浆cf-mtDNA和GDF15水平。统计分析包括Wilcoxon sign -rank检验、Spearman相关性检验和Mann-Whitney检验。结果：血浆cf-mtDNA水平在妊娠期间无显著差异，而血浆GDF15水平从妊娠早期到晚期升高，产后降低。妊娠晚期血浆GDF15与孕前BMI （p = 0.035）和出生时胎龄（p = 0.0048）呈负相关。结论：本研究在两个国家的研究中发现了围产期血浆中cf-mtDNA和GDF15水平的不同模式，将这些线粒体标志物与孕产妇痛苦和妊娠结局联系起来。

{"title":"Mitochondrial health, prenatal distress, and gestational age: investigation of cf-mtDNA and GDF15 in two pregnancy studies from the USA and Turkey","authors":"Qiuhan Huang , David Shire , Fiona Hollis , Sameera Abuaish , Martin Picard , Catherine Monk , Elif Aysimi Duman , Caroline Trumpff","doi":"10.1016/j.mito.2025.102057","DOIUrl":"10.1016/j.mito.2025.102057","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for energy production and stress adaptation, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey.</div></div><div><h3>Methods</h3><div>We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N = 187, USA) and BABIP (N = 198, Turkey). Data were collected at multiple timepoints during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4–14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests.</div></div><div><h3>Results</h3><div>Plasma cf-mtDNA levels did not significantly vary across pregnancy, while plasma GDF15 levels increased from early to late pregnancy and decreased postpartum. Late 2nd trimester plasma GDF15 was negatively correlated with pre-pregnancy BMI (p = 0.035) and gestational age (p = 0.0048) at birth. Early 2nd trimester maternal distress was associated with lower cf-mtDNA (all p-values < 0.05) and a trend for lower GDF15. Higher pre-pregnancy BMI and late-pregnancy maternal distress were linked to smaller postpartum GDF15 declines in EPI (all p-values < 0.05).</div></div><div><h3>Conclusions</h3><div>This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, linking these mitochondrial markers to maternal distress and pregnancy outcomes.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"84 ","pages":"Article 102057"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the microRNA-mitochondrial nexus in hepatocellular carcinoma 探索肝细胞癌中的微 RNA-线粒体关系

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-04-24 DOI: 10.1016/j.mito.2025.102045

Ali Jawad Akki , Srinivas Nanduri , Shankargouda V Patil , Kusal K Das , Prachi Parvatikar

MicroRNAs (miRNAs) are double-edged swords in hepatocellular carcinoma (HCC) that play a dual role in disease progression and suppression. The pivotal role of miRNAs in gene regulation emphasizes their potential to disrupt critical cellular processes, including mitochondrial function. Given the indispensable role of mitochondria in energy production, apoptosis, and metabolic control, all of which are central to HCC progression, understanding the miRNA-mitochondria axis is crucial. MiRNAs emerge as pivotal regulators of mitochondrial function, exerting profound influence over HCC progression. This comprehensive review delves into the multifaceted roles of miRNAs in modulating mitochondrial biogenesis, dynamics, and apoptosis. MiRNA impacts key metabolic pathways, including energy metabolism, fatty acid metabolism, and oxidative stress. The intricate interplay between miRNAs and mitochondrial function extends to the regulation of mitophagy and ferroptosis. By exploring the microRNA-mitochondrial axis, this review offers insights for identifying novel diagnostic and therapeutic targets.

MicroRNAs （miRNAs）在肝细胞癌（HCC）中是一把双刃剑，在疾病进展和抑制中发挥双重作用。mirna在基因调控中的关键作用强调了它们破坏关键细胞过程的潜力，包括线粒体功能。鉴于线粒体在能量产生、细胞凋亡和代谢控制中不可或缺的作用，所有这些都是HCC进展的核心，了解mirna -线粒体轴是至关重要的。mirna是线粒体功能的关键调节因子，对HCC的进展具有深远的影响。这篇综合综述深入研究了mirna在调节线粒体生物发生、动力学和凋亡中的多方面作用。MiRNA影响关键的代谢途径，包括能量代谢、脂肪酸代谢和氧化应激。mirna和线粒体功能之间复杂的相互作用延伸到线粒体自噬和铁下垂的调节。通过对microrna -线粒体轴的探索，本综述为确定新的诊断和治疗靶点提供了新的见解。

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引用次数: 0

MiR-718-mediated inhibition of prohibitin 1 influences mitochondrial dynamics, proliferation, and migration of keratinocytes mir -718介导的禁止素1抑制影响线粒体动力学、增殖和角化细胞的迁移

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-04-17 DOI: 10.1016/j.mito.2025.102041

Himani Rani , Neeru Saini

Keratinocyte hyperproliferation is a key characteristic of psoriasis. Prohibitins (PHB) are known to be associated with keratinocyte proliferation and cell cycle regulation, influenced by mitochondrial processes. The objective of this study was to examine the impact of miR-718 overexpression and downregulation on the various PHB1-mitochondria-driven activities in HaCaT keratinocytes. We demonstrated that PHB1 expression is downregulated through direct targeting by miR-718, which then leads to a reduction in the expression of MFN1, MFN2, and OPA1 in miR-718-transfected cells, as evidenced by western blot analysis. Mitochondrial fusion and DRP1-mediated fission, as indicated by western blot results, were further validated using confocal imaging with CMXRoS labeling, contrasting with the effects of AM-718. JC-1 dye staining results demonstrated the miR-718 overexpression facilitates the mitochondrial membrane depolarization that highlighting the PHB1-OPA1 mediated depolarization. Moreover, OPA1 maintains mitochondrial cristae structure and its dysfunction can trigger cell death. Further PHB1 is known to regulate OPA1 function, alters mitochondrial morphology and significantly influences epithelial cell migration. Herein, our data demonstrated a reduction in keratinocyte proliferation and migration, as evidenced by the CCK assay and wound healing assay, respectively, following 24 h of transfection. Ultimately, our data indicates the potential involvement of miR-718 in the mitochondria-mediated suppression of cell proliferation and migration in HaCaT keratinocytes, likely due to modified mitochondrial processes via PHB1.

角质细胞过度增殖是银屑病的一个主要特征。众所周知，抑制素（PHB）与角质细胞增殖和细胞周期调节有关，并受线粒体过程的影响。本研究的目的是研究 miR-718 的过表达和下调对 HaCaT 角质细胞中 PHB1 线粒体驱动的各种活动的影响。我们证明，通过 miR-718 的直接靶向作用，PHB1 的表达被下调，进而导致 miR-718 转染细胞中 MFN1、MFN2 和 OPA1 的表达减少，这一点已在 Western 印迹分析中得到证实。线粒体融合和 DRP1 介导的裂变（如 Western 印迹结果所示）通过 CMXRoS 标记的共聚焦成像得到了进一步验证，与 AM-718 的效果形成了鲜明对比。JC-1 染料染色结果表明，miR-718 的过表达促进了线粒体膜去极化，突出了 PHB1-OPA1 介导的去极化。此外，OPA1 可维持线粒体嵴结构，其功能障碍可引发细胞死亡。此外，已知 PHB1 可调节 OPA1 的功能、改变线粒体形态并显著影响上皮细胞的迁移。在此，我们的数据表明，转染 24 小时后，角质形成细胞的增殖和迁移均有所减少，CCK 试验和伤口愈合试验分别证明了这一点。最终，我们的数据表明，miR-718 可能参与了线粒体介导的抑制 HaCaT 角质细胞增殖和迁移的过程，这可能是由于通过 PHB1 改变了线粒体过程。

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引用次数: 0

Ultrastructural and functional recovery of mitochondria and improved developmental competence by melatonin in oxidatively stressed porcine oocytes 褪黑素对氧化应激猪卵母细胞线粒体超微结构和功能的恢复及发育能力的改善

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-09-01 Epub Date: 2025-06-19 DOI: 10.1016/j.mito.2025.102060

Heyyoung Kim , Seonggyu Bang , Ayeong Han , Heejae Kang , Islam M. Saadeldin , Ahmad Yar Qamar , Sanghoon Lee , Jongki Cho

Mitochondrial dysfunction induced by oxidative stress impairs oocyte maturation and subsequent embryonic development. In this study, we investigated whether melatonin, a potent antioxidant, could mitigate hydrogen peroxide (H₂O₂)-induced mitochondrial damage in porcine oocytes and restore their developmental competence. Oocytes were exposed to H₂O₂ prior to in vitro maturation (IVM), followed by treatment with varying concentrations of melatonin (0, 0.5, 1, and 5 μM). Melatonin treatment significantly improved maturation and blastocyst formation rates, with 1 μM showing the most pronounced effect. This recovery was accompanied by enhanced mitochondrial bioenergetics, which was likely driven by reduced ROS accumulation and increased intracellular glutathione. Melatonin also reversed the ultrastructural abnormalities of mitochondria, reduced apoptotic signals, and normalized mitophagy markers. These findings suggest that melatonin confers mitochondrial protection and promotes oocyte competence under oxidative stress, supporting its therapeutic potential in reproductive biotechnology.

氧化应激诱导的线粒体功能障碍损害卵母细胞成熟和随后的胚胎发育。在这项研究中，我们研究了褪黑激素（一种有效的抗氧化剂）是否可以减轻过氧化氢（H2O2）诱导的猪卵母细胞线粒体损伤，并恢复其发育能力。卵母细胞在体外成熟（IVM）之前暴露于H2O2中，然后用不同浓度的褪黑激素（0、0.5、1和5 μM）处理。褪黑素治疗显著提高了成熟和囊胚形成率，其中以1 μM效果最显著。这种恢复伴随着线粒体生物能量的增强，这可能是由ROS积累减少和细胞内谷胱甘肽增加所驱动的。褪黑素还能逆转线粒体超微结构异常，减少凋亡信号，并使线粒体自噬标记物正常化。这些发现表明，褪黑激素赋予线粒体保护并促进氧化应激下的卵母细胞能力，支持其在生殖生物技术中的治疗潜力。

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引用次数: 0

The compound XueShuanTong promotes podocyte mitochondrial autophagy via the AMPK/mTOR pathway to alleviate diabetic nephropathy injury 复方血栓通通过AMPK/mTOR通路促进足细胞线粒体自噬，减轻糖尿病肾病损伤。

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-07-01 Epub Date: 2025-03-03 DOI: 10.1016/j.mito.2025.102024

Chuangbiao Zhang , Weiwei Ren , Xiaohua Lu , Lie Feng , Jiaying Li , Beibei Zhu

The study aimed to elucidate the molecular mechanisms underlying the protective effects of Compound Xueshuantong (CXst) in the context of diabetic nephropathy (DN), a major cause of kidney failure driven by podocyte injury and metabolic dysfunction. Given the critical role of the AMPK/mTOR signaling pathway in regulating cellular energy balance, autophagy, and mitochondrial health, we focused on its involvement in podocyte function and how it might be influenced by CXst. Through a series of experiments, we found that CXst treatment led to the upregulation of key proteins involved in autophagy, such as LC3 and p62, as well as proteins critical for mitochondrial function, like PGC-1α. These molecular changes helped to counteract the damaging effects of high glucose levels on podocytes, which are central to maintaining the filtration function of the kidneys. Additionally, CXst’s ability to modulate the AMPK/mTOR pathway was shown to be a pivotal factor in its protective effects, as inhibition of AMPK significantly reduced these benefits. This comprehensive study provides strong evidence that CXst exerts its protective effects against DN by modulating the AMPK/mTOR pathway, thus preserving podocyte integrity and function. These findings suggest that CXst could be a promising candidate for the development of new therapeutic strategies for the treatment of DN, offering hope for better management of this challenging condition.

本研究旨在阐明复方血栓通（CXst）对糖尿病肾病（DN）保护作用的分子机制，糖尿病肾病是由足细胞损伤和代谢功能障碍引起的肾衰竭的主要原因。鉴于AMPK/mTOR信号通路在调节细胞能量平衡、自噬和线粒体健康方面的关键作用，我们关注其参与足细胞功能以及它如何受到CXst的影响。通过一系列实验，我们发现CXst处理导致参与自噬的关键蛋白上调，如LC3和p62，以及对线粒体功能至关重要的蛋白，如PGC-1α。这些分子变化有助于抵消高葡萄糖水平对足细胞的破坏性影响，足细胞是维持肾脏过滤功能的核心。此外，CXst调节AMPK/mTOR通路的能力被证明是其保护作用的关键因素，因为AMPK的抑制显著降低了这些益处。这项全面的研究提供了强有力的证据，证明CXst通过调节AMPK/mTOR通路发挥其对DN的保护作用，从而保持足细胞的完整性和功能。这些发现表明，CXst可能是开发新的DN治疗策略的有希望的候选者，为更好地管理这一具有挑战性的疾病提供了希望。

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引用次数: 0