Mitochondrion最新文献_第6页

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 : 2025-05-04 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

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 : 2025-04-24 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

Mitochondrial transplantation: Triumphs, challenges, and impacts on nuclear genome remodelling 线粒体移植：胜利、挑战和对核基因组重塑的影响

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-04-18 DOI: 10.1016/j.mito.2025.102042

Elly H. Shin , Quinn Le , Rachel Barboza , Amanda Morin , Shiva M. Singh , Christina A. Castellani

Mitochondria are membrane-bound organelles of eukaryotic cells that play crucial roles in cell functioning and homeostasis, including ATP generation for cellular energy. Mitochondrial function is associated with several complex diseases and disorders, including cardiovascular, cardiometabolic, neurodegenerative diseases and some cancers. The risk for these diseases and disorders is often associated with mitochondrial dysfunction, particularly the quantitative and qualitative features of the mitochondrial genome. Emerging results implicate mito-nuclear crosstalk as the mechanism by which mtDNA variation affects complex disease outcomes. Experimental approaches are emerging for the targeting of mitochondria as a potential therapeutic for several of these diseases, particularly in the form of mitochondrial transplantation. Current approaches to mitochondrial transplantation generally involve isolating healthy mitochondria from donor cells and introducing them to diseased recipients towards amelioration of mitochondrial dysfunction. Using such a protocol, several reports have shown recovery of mitochondrial function and improved disease outcomes post-mitochondrial transplantation, highlighting its potential as a therapeutic method for several complex, severe and debilitating diseases. Additionally, the mitochondrial genome can be modified prior to transplantation to target disease-associated site-specific mutations and to reduce the ratio of mutant-to-WT alleles. These promising results may underlie the potential impact of mitochondrial transplantation on mito-nuclear genome interactions in the setting of the disease. Further, we recommend that mitochondrial transplantation experimentation include an assessment of potential impacts on remodelling of the nuclear genome, particularly the nuclear epigenome and transcriptome. Herein, we review these and other triumphs and challenges of mitochondrial transplantation as a potential novel therapeutic for mitochondria-associated diseases.

线粒体是真核细胞的膜结合细胞器，在细胞功能和稳态中起着至关重要的作用，包括生成细胞能量的ATP。线粒体功能与几种复杂的疾病和失调有关，包括心血管、心脏代谢、神经退行性疾病和一些癌症。这些疾病和失调的风险通常与线粒体功能障碍有关，特别是线粒体基因组的定量和定性特征。新出现的结果暗示有丝分裂核串扰是mtDNA变异影响复杂疾病结果的机制。以线粒体为靶点的实验方法正在出现，作为几种这些疾病的潜在治疗方法，特别是以线粒体移植的形式。目前的线粒体移植方法通常涉及从供体细胞中分离健康线粒体，并将其引入患病受体，以改善线粒体功能障碍。使用这样的方案，一些报告显示线粒体移植后线粒体功能的恢复和疾病预后的改善，突出了其作为几种复杂、严重和衰弱性疾病的治疗方法的潜力。此外，可以在移植前对线粒体基因组进行修饰，以靶向疾病相关的位点特异性突变，并降低突变型与wt等位基因的比例。这些有希望的结果可能是线粒体移植对线粒体核基因组相互作用的潜在影响的基础。此外，我们建议线粒体移植实验包括对核基因组，特别是核表观基因组和转录组重塑的潜在影响的评估。在此，我们回顾了线粒体移植作为线粒体相关疾病的潜在新治疗方法的这些成就和其他挑战。

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引用次数: 0

Cell-specific mitochondrial response in progressive supranuclear palsy 进行性核上性麻痹的细胞特异性线粒体反应

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-04-18 DOI: 10.1016/j.mito.2025.102043

Valerie Sackmann , Nasna Nassir , Satoshi Tanikawa , Shelley L. Forrest , Helen Chasiotis , Jun Li , Shehzad Hanif , Ivan Martinez-Valbuena , Maria Carmela Tartaglia , Anthony E. Lang , Mohammed Uddin , Alexei Verkhratsky , Gabor G. Kovacs

Progressive supranuclear palsy (PSP) is a main form of idiopathic tauopathy characterized neuropathologically by subcortical neurofibrillary tangles in neurons, oligodendroglial coiled bodies, and tufted astrocytes, which follow sequential distribution in the human brain. Mitochondrial dysfunction is thought to be a contributor to many neurodegenerative diseases, but its role in PSP at the cellular level remains incompletely understood. To address this, we performed cell-specific morphometric analysis of mitochondrial markers in post-mortem tissues from motor cortex of PSP patients and non-diseased controls (n = 5 each) followed by single-nuclear transcriptomics (n = 3 each) to identify changes in genes that regulate mitochondrial function. We treated iCell astrocytes with PSP brain homogenates and isolated viable astrocytes from multiple regions of PSP-affected brains. We found that PSP is characterized by significant mitochondrial changes in neurons and astrocytes at the immunohistochemical level, particularly in complex I, with distinct transcriptomic responses across cell types. Glial cells exhibited upregulation of pathways associated with mitochondrial function. In contrast, excitatory and inhibitory neurons showed downregulation in these pathways, indicating impaired mitochondrial function. Astrocytes derived from different human brain regions express varied levels of GFAP and EAAT1 immunoreactivity. Astrocytic tau pathology in cell culture derived from postmortem PSP brains mirrors that seen in corresponding brain tissue histology. Tau pathology in human astrocyte cell culture is associated with clumps of mitochondria potentially associated with impairment in their neuron supportive function. Our results underscore selective complex I damage and cell-type specific patterns that differentiate PSP from other neurodegenerative diseases.

进行性核上麻痹（PSP）是特发性脑病的一种主要形式，其神经病理学特征是神经元皮层下神经原纤维缠结、少突胶质卷曲体和丛状星形胶质细胞，它们在人脑中顺序分布。线粒体功能障碍被认为是许多神经退行性疾病的一个因素，但其在PSP细胞水平上的作用仍不完全清楚。为了解决这个问题，我们对PSP患者和非患病对照组（各n = 5）的死后组织中的线粒体标记物进行了细胞特异性形态计量学分析，然后进行了单核转录组学（各n = 3），以确定调节线粒体功能的基因的变化。我们用PSP脑匀浆处理iCell星形胶质细胞，并从PSP脑的多个区域分离出有活力的星形胶质细胞。我们发现PSP的特点是在免疫组织化学水平上神经元和星形胶质细胞的线粒体发生显著变化，特别是在复合物I中，不同细胞类型的转录组反应不同。胶质细胞表现出与线粒体功能相关的通路上调。相反，兴奋性和抑制性神经元在这些通路中表现出下调，表明线粒体功能受损。来源于人脑不同区域的星形胶质细胞表达不同水平的GFAP和EAAT1免疫反应性。死后PSP脑细胞培养的星形细胞tau病理学反映了相应的脑组织组织学。人类星形胶质细胞培养中的Tau病理与线粒体团块可能与神经元支持功能受损相关。我们的结果强调了选择性复合物I损伤和细胞类型特异性模式，将PSP与其他神经退行性疾病区分开来。

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引用次数: 0

Mitochondrial quality control and stress signaling pathways in the pathophysiology of cardio-renal diseases 心肾疾病病理生理中的线粒体质量控制和应激信号通路

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-04-17 DOI: 10.1016/j.mito.2025.102040

Isabel Amador-Martínez , Ana Karina Aranda-Rivera , Mauricio Raziel Martínez-Castañeda , José Pedraza-Chaverri

Mitochondria are essential organelles for cellular function and have become a broad field of study. In cardio-renal diseases, it has been established that mitochondrial dysfunction is a primary mechanism leading to these pathologies. Under stress, mitochondria can develop stress response mechanisms to maintain mitochondrial quality control (MQC) and functions. In contrast, the perturbation of these mechanisms has been associated with the pathogenesis of several diseases. Thus, targeting specific pathways within MQC could offer a therapeutic avenue for protecting mitochondrial integrity. However, the mechanisms related to MQC and mitochondrial stress signaling in the cardio-renal axis have been poorly explored. The primary limitations include the lack of reproducibility in the experimental models of cardio-renal disease, the incomplete knowledge of molecules that generate bidirectional damage, and the temporality of the study models. Therefore, we believe that integration of all of those limitations, along with recent advances in MQC mechanisms (i.e., mitophagy), stress signaling pathways (e.g., integrated stress response, mitochondrial unfolded protein response, and mitochondrial protein import), associated pharmacology, and targeted therapeutic approaches could reveal what the deregulation of these mechanisms is like and provide ideas for generating strategies that seek to avoid the progression of cardio-renal diseases.

线粒体是细胞功能的重要细胞器，已成为一个广泛的研究领域。在心肾疾病中，已经确定线粒体功能障碍是导致这些病理的主要机制。在应激条件下，线粒体可以发展应激反应机制，维持线粒体质量控制（MQC）和功能。相反，这些机制的扰动与几种疾病的发病机制有关。因此，靶向MQC中的特定途径可能为保护线粒体完整性提供治疗途径。然而，与MQC和线粒体应激信号有关的机制在心肾轴上的探索很少。主要的限制包括心肾疾病的实验模型缺乏可重复性，对产生双向损伤的分子的不完全了解，以及研究模型的临时性。因此，我们相信，整合所有这些局限性，以及MQC机制（即，线粒体自噬），应激信号通路（例如，综合应激反应，线粒体未折叠蛋白反应和线粒体蛋白输入），相关药理学和靶向治疗方法的最新进展，可以揭示这些机制的放松管制是什么样的，并为产生寻求避免心肾疾病进展的策略提供思路。

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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 : 2025-04-17 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

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 : 2025-04-07 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

Kinetic characterization of respirasomes and free complex I from Yarrowia lipolytica 脂溶耶氏菌呼吸小体和游离复合体I的动力学特性

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-04-01 DOI: 10.1016/j.mito.2025.102035

Giovanni García-Cruz, Mercedes Esparza-Perusquía, Alejandro Cruz-Cárdenas, Diana Cruz-Vilchis, Oscar Flores-Herrera

The mitochondrion is a highly dynamic organelle capable of adapting to external stimuli and the energetic demands of the cell. As the primary source of cellular ATP, generating approximately 90 % of the total, mitochondrion facilitates the association of respiratory complexes I, III₂, and IV into supramolecular structures called respirasomes. This supramolecular organization enhances protein density within the mitochondrial inner membrane, enabling homogenous energy production. In this study, we investigate the subunits composition and the kinetic characterization of digitonin-solubilized respirasomes and the free complex I from Yarrowia lipolytica as well as their role in reactive oxygen species (ROS) production. The NADH:DBQ oxido reductase activity of respirasome and free complex I was similar. Respiration by respirasome was inhibited with rotenone, antimycin A, or cyanide, simultaneously to an increase in the ROS production. A value of 1.6 ± 0.2 for the NADH oxidized/oxygen reduced ratio was determined for the respirasome activity. The role of interaction between complexes in the function of the respirasome is discussed.

线粒体是一种高度动态的细胞器，能够适应外部刺激和细胞的能量需求。线粒体是细胞ATP的主要来源，约占总量的90%，它促进呼吸复合物I、III2和IV结合成称为呼吸小体的超分子结构。这种超分子组织增强了线粒体内膜内的蛋白质密度，使能量产生均匀性。在这项研究中，我们研究了洋地黄苷溶解的呼吸小体和游离复合物I的亚基组成和动力学特征，以及它们在活性氧（ROS）产生中的作用。呼吸小体和游离复合体I的NADH:DBQ氧化还原酶活性相似。鱼藤酮、抗霉素A或氰化物抑制呼吸小体的呼吸作用，同时增加ROS的产生。测定呼吸小体活性的NADH氧化/氧还原比值为1.6±0.2。讨论了复合体之间的相互作用在呼吸小体功能中的作用。

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引用次数: 0

An inherited mtDNA rearrangement, mimicking a single large-scale deletion, associated with MIDD and a primary cardiological phenotype 模仿单个大规模缺失的遗传性 mtDNA 重排，与 MIDD 和原发性心脏病表型相关。

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-03-29 DOI: 10.1016/j.mito.2025.102037

Piervito Lopriore , Andrea Legati , Christiane Michaela Neuhofer , Annalisa Lo Gerfo , Robert Kopajtich , Marco Barresi , Giulia Cecchi , Martin Pavlov , Rossella Izzo , Vincenzo Montano , Maria Adelaide Caligo , Riccardo Berutti , Michelangelo Mancuso , Holger Prokisch , Daniele Ghezzi

Aim

To identify the genetic cause in a previously unsolved pedigree, with mother and two daughters suffering of dilated cardiomyopathy with prevailing arrhythmic burden associated with diabetes mellitus and sensorineural hearing loss, without clear evidence of progressive external ophthalmoplegia.

Methods

Several genetic tests were performed over the years including single-gene sequencing, mitochondrial DNA (mtDNA) sequencing, NGS panel for mitochondrial diseases and cardiomyopathies, clinical exome sequencing and whole exome sequencing. Specific amplifications and long-read NGS were used to evaluate mtDNA structural alterations.

Results

By means of whole exome sequencing we found a novel heteroplasmic 12 kb-long single deletion in the mtDNA in all affected family members, confirmed by long-range PCR. However, a deeper investigation by long-read NGS revealed indeed the presence of rearranged mtDNA species, formed by a wild-type plus a deleted molecule. This mtDNA duplication turned out to be inherited in our pedigree and present in all tested specimens.

Conclusion

While mtDNA single large-scale deletions are generally considered sporadic, few old reports described maternally inherited mtDNA duplication We suggest that mtDNA large rearrangements should be considered as possible disease causes in familial cases with unusual mitochondrial phenotypes. Long-read sequencing is useful for the detection of these variants, particularly mtDNA duplications.

目的：在一个以前未解决的谱系中，确定遗传原因，母亲和两个女儿患有扩张性心肌病，伴有普遍的心律失常负担，与糖尿病和感音神经性听力损失有关，没有明确的进行性外眼麻痹的证据。方法：多年来进行了多项基因检测，包括单基因测序、线粒体DNA （mtDNA）测序、线粒体疾病和心肌病的NGS面板、临床外显子组测序和全外显子组测序。特异性扩增和长读NGS用于评估mtDNA结构改变。结果：通过全外显子组测序，我们在所有患病家族成员的mtDNA中发现了一个新的异质12 kb长的单缺失，并通过远程PCR证实。然而，NGS的一项更深入的调查显示，确实存在由野生型和缺失分子组成的重排mtDNA物种。这种mtDNA复制在我们的谱系中被证明是遗传的，并存在于所有测试样本中。结论：虽然mtDNA单次大规模缺失通常被认为是零星的，但很少有古老的报道描述了母系遗传的mtDNA重复。我们建议，在线粒体表型异常的家族性病例中，mtDNA大规模重排应被认为是可能的疾病原因。长读测序对于检测这些变异，特别是mtDNA重复是有用的。

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引用次数: 0

Perceived association of mood and symptom severity in adults with mitochondrial diseases 成人线粒体疾病患者情绪与症状严重程度的感知关联

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion

Pub Date : 2025-03-29 DOI: 10.1016/j.mito.2025.102033

Catherine Kelly , Marissa Cross , Alex Junker , Kris Englestad , Xiomara Q. Rosales , Michio Hirano , Caroline Trumpff , Martin Picard

Individuals with genetic mitochondrial diseases suffer from multisystem symptoms that vary in severity and over time, but the factors influencing disease manifestations are poorly understood. Based upon i) patient and family reports that stressful life events trigger or exacerbate symptoms, ii) biologically plausible pathways whereby psychological states and stress hormones influence mitochondrial energy transformation capacity, and iii) epidemiological literature linking traumatic/stressful life events and multiple neurologic disorders, we hypothesized that mitochondrial disease symptom severity may in part vary with daily mood. To examine patients’ perception around potential psycho-biological mechanisms known to operate in other chronic illnesses, we administered the Stress, Health and Emotion Survey (SHES) to 70 adults with self-reported mitochondrial diseases. Participants rated how severe each of their symptom(s) was over the past year, separately for either ‘good’ (happy, calm) or ‘bad’ (stress, sad) emotional days. On average, patients reported that most symptoms were better on “good” emotional days (p < 0.0001) and worse on “bad” emotional days (p < 0.0001). Of the 29 symptoms assessed, 27 were associated with daily mood (p < 0.01). Some but not all symptoms were reported to be less or more severe on good and bad days, respectively, including fatigue, exercise intolerance, brain fog, and fine motor coordination (ps < 0.0001). These associative results suggest that on average individuals living with mitochondrial diseases perceive a connection between their mood and symptoms severity. These preliminary findings constitute an initial step towards developing more comprehensive models to understand the psychobiological factors that influence the course of mitochondrial diseases.

患有遗传性线粒体疾病的个体患有多系统症状，其严重程度和时间不同，但影响疾病表现的因素知之甚少。基于i)患者和家属报告的应激性生活事件触发或加重症状，ii)心理状态和应激激素影响线粒体能量生产能力的生物学可信途径，以及iii)将创伤/应激性生活事件与多种神经系统疾病联系起来的流行病学文献，我们假设线粒体疾病症状的严重程度可能部分随日常情绪而变化。为了检查患者对已知在其他慢性疾病中起作用的潜在心理生物学机制的看法，我们对70名自我报告患有线粒体疾病的成年人进行了压力、健康和情绪调查（SHES）。参与者对过去一年中他们的症状的严重程度进行了评估，分别是“好”（快乐、平静）和“坏”（压力、悲伤）情绪的日子。平均而言，患者报告说，在情绪“良好”的日子里，大多数症状都有所好转

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引用次数: 0