线粒体自噬与骨质疏松症

骨质疏松症是增龄性疾病,尤其是绝经后妇女最为常见。骨稳态失衡在骨质疏松症的发生、发展中有着重要作用。作为细胞重要的防御和应激调控机制,自噬与骨稳态的维持有着密不可分的关系。线粒体自噬是自噬的一种途径,主要通过清除受损的线粒体,降低细胞内活性氧(reactive oxygen species, ROS)水平,维持细胞活性。已有研究表明,线粒体自噬与骨稳态密切相关。本文就近年线粒体自噬与骨质疏松症相关性研究进行综述,希望在该研究领域梳理一些新的思路、启发一些新的思维。     

线粒体自噬和内质网应激调控血管内皮细胞功能研究进展

血管内皮细胞在调节人体血液循环功能、维持人体心血管系统稳定及促进血管结构重塑中发挥着重要作用。近年来的研究成果证实,线粒体自噬与人体血管壁、内皮组织细胞氧化稳态和细胞氧化应激机制关系密切。内质网是一种维持人体细胞内部结构和生理功能的重要亚特性细胞器,参与人体细胞的众多自然生理化学活动。多种细胞刺激化学因素作用造成的内质网应激能直接诱导人体细胞自噬,并能通过多种化学途径直接影响细胞线粒体的组织形态与细胞功能。研究表明,内质网应激在动脉粥样硬化等血管损伤相关疾病中扮演重要角色。本文重点介绍了内质网应激和线粒体自噬对血管内皮细胞功能的调控作用,简要分析了内质网应激和线粒体自噬的相互关系,旨在为进一步研究线粒体自噬和内质网应激调控血管内皮细胞的分子机制提供参考。     

线粒体自噬在COPD发病机制中作用的研究进展

慢性阻塞性肺疾病(COPD)是最常见的呼吸系统疾病之一.自噬是内质网膜包裹并降解异常蛋白质和细胞器的细胞途径,对维持细胞正常生理功能至关重要.线粒体是细胞中最重要的细胞器,主要参与能量生成和氧化还原反应等重要细胞过程.线粒体自噬是一种选择性清除损伤线粒体的自噬过程,是维持线粒体功能和数量正常的重要途径.越来越多的研究发现,线粒体自噬在COPD的病理生理过程中发挥着重要作用,故本文将线粒体自噬在COPD发病机制中的作用进行综述.     

线粒体自噬与心脏能量代谢研究进展

<正>线粒体是真核细胞能量产生的主要场所,其通过氧化磷酸化的形式为机体提供ATP,维持细胞的基础代谢。外界刺激或病理环境可导致线粒体结构和功能受损,最终导致ATP合成受限。线粒体自噬通过选择性清除该类功能障碍线粒体,保持细胞内线粒体数量的平衡性、结构和功能的完整性,维持细胞内环境稳态,并促进细胞的存活,对保证机体的能量供应至关重要。近年研究表明,线粒体自噬异常会导     

线粒体质量控制在2型糖尿病发生发展及治疗中的作用研究进展

线粒体作为细胞能量代谢的核心参与者，参与了胰岛素抵抗和2型糖尿病发生机制。线粒体质量控制系统包括线粒体生物合成、线粒体动力学、线粒体自噬。线粒体质量控制通过不断融合/分裂改变其形状及大小、生物合成新生线粒体补充线粒体池和自噬将包裹受损的线粒体传递至溶酶体进行清除，维持相对稳定的线粒体数量和质量的动态过程，是保证线粒体健康和维持线粒体稳态的重要机制。糖尿病患者在线粒体自噬、动力学和生物合成方面存在缺陷，即线粒体质量控制失调，导致线粒体功能障碍，诱发β细胞功能紊乱甚至死亡。深入了解线粒体质量控制与T2DM的关系，通过调节线粒体生物合成、线粒体融合/分裂和线粒体自噬等相关因子表达，影响线粒体质量控制，从而改善外周组织的胰岛素敏感性、提高葡萄糖刺激胰岛素分泌能力、促进白色脂肪褐变和减少脂肪异位沉积，达到降糖、降脂、治疗T2DM的目的。     

自噬在糖尿病肾病发病机制中的作用

自噬是真核细胞内维持细胞内环境稳定的重要内降解机制,作用在通过溶酶体蛋白的降解,清除受损的结构或过度表达的蛋白,参与维持细胞更新和细胞内稳态。经研究发现,自噬主要通过参与炎症反应、内质网应激及线粒体功能障碍等过程,影响糖尿病肾病的发生发展。该文现就自噬的分子机制,糖尿病肾病与自噬相关研究的新进展进行综述。从而为糖尿病肾病的机制研究及治疗提供新思路。     

线粒体自噬与心血管疾病

<正>1线粒体自噬线粒体是一种双层膜封闭式细胞器,其组成约占总细胞体积的30%,同时也是细胞最敏感的细胞器之一。线粒体不仅能通过氧化呼吸链产生大量三磷酸腺苷(ATP)以维持心肌正常的电生理和收缩功能,还参与调节胞内钙稳态、活性氧的生成及启动多种信号分子等,因此,适时清除受损伤的线粒体对于细胞的正常生长和代谢具有重要作用。线粒体自噬是指在各种外界刺激作用下发生损伤的线粒体被特异性的包裹进自噬体中,与溶酶体融合并完成损     

线粒体稳态在糖尿病心肌病发生发展中作用的研究进展

糖尿病心肌病是一种发生于糖尿病患者中与冠状动脉疾病等其他心肌病无关的心脏功能障碍, 是导致糖尿病患者心力衰竭及最终死亡的重要原因。糖尿病心肌病的发病机制主要包括氧化应激、炎症反应、细胞凋亡和线粒体稳态失调等。线粒体稳态主要包括线粒体动力学、线粒体氧化代谢和线粒体自噬, 其受多种信号通路的调控, 在维持心肌细胞正常功能中发挥重要作用, 若线粒体稳态失调则会引发氧化应激乃至心肌细胞线粒体网络破碎, 导致脂肪酸累积, 加速糖尿病心肌病的发展。目前, 糖尿病心肌病的发病机制尚未明确, 缺少有效的预防和治疗方法, 该文从线粒体稳态方向阐述糖尿病心肌病发病机制, 为临床治疗提供新的思路和策略。     

线粒体DNA在慢性肝病发病机制中作用的研究进展

线粒体DNA是位于线粒体基质内线粒体自有的遗传物质,参与细胞代谢和能量供给。线粒体DNA的损伤通过增加活性氧的释放加剧氧化应激,线粒体DNA释放亦可引发细胞凋亡及通过损伤相关分子模式激活免疫炎症反应。线粒体自噬则通过负反馈机制调控线粒体DNA损伤和释放,维持细胞内稳态。近年研究结果显示,慢性肝病的发生、发展与线粒体DN...     

自噬与氧化应激对青光眼视神经损伤的调节作用研究进展

视网膜神经节细胞（RGCs）具有长轴突和高密度线粒体,因而对氧化应激更加敏感。细胞内产生的活性氧（ROS）与青光眼的发病机制密切相关。自噬是细胞内一种质量控制系统,可以去除氧化的细胞成分,维持细胞稳态。在各种青光眼视神经损害模型中,氧化应激被激活,ROS通过雷帕霉素靶蛋白通路启动自噬;接着自噬通过促进RGCs线粒体自噬和抗氧化反应减少ROS的积聚。然而当视神经中仍有过量的ROS则会抑制自噬发生,因为多余的ROS会破坏线粒体功能、氧化自噬相关蛋白和降低自噬溶酶体活性,导致青光眼视神经的变性。ROS与自噬相互影响,二者共同参与青光眼视神经损害过程。     

线粒体TOM系统在心血管疾病中的研究现状

线粒体内稳态的维持与其内部蛋白密切相关,而绝大多数蛋白进入线粒体内部发挥作用均需通过线粒体的线粒体外膜转位酶(translocase of the outer mitochondrial membrane,TOM)系统的转运。研究表明,线粒体TOM系统相关组成亚基Tom70、Tom20和Tom40等参与了心血管疾病的发生发展,这为我们从线粒体蛋白水平研究心血管疾病的机制及开发新的治疗措施提供了思路。本文针对线粒体TOM系统在心血管相关疾病(如心肌缺血/再灌注、高血压及心功能衰竭)方面的研究现状进行了综述。     

Mitochondrial dynamics: Orchestrating the journey to advanced age

Aging is a degenerative process that unfortunately is an inevitable part of life and risk factor for cardiovascular disease including heart failure. Among the several theories purported to explain the effects of age on cardiac dysfunction, the mitochondrion has emerged a central regulator of this process. Hence, it is not surprising that abnormalities in mitochondrial quality control including biogenesis and turnover have such detrimental effects on cardiac function. In fact mitochondria serve as a conduit for biological signals for apoptosis, necrosis and autophagy respectively. The removal of damaged mitochondria by autophagy/mitophagy is essential for mitochondrial quality control and cardiac homeostasis. Defects in mitochondrial dynamism fission/fusion events have been linked to cardiac senescence and heart failure. In this review we discuss the impact of aging on mitochondrial dynamics and senescence on cardiovascular health. This article is part of a Special Issue entitled: CV Aging.     

线粒体及其蛋白质质量控制失调与动脉粥样硬化的关系

线粒体是哺乳动物细胞内重要的细胞器,作为细胞能量代谢和细胞死亡的调控中心,其功能异常会导致多种疾病的发生与发展。 线粒体功能依赖于线粒体蛋白质组的完整性和稳态,因此线粒体蛋白质质量控制系统对于维持线粒体稳态和机体健康十分重要。当线粒体及其蛋白质质量控制系统出现异常时,会直接损伤线粒体并出现异常线粒体蛋白堆积,发生细胞内环境紊乱,甚至细胞功能障碍,进而影响动脉粥样硬化性疾病的发生与发展。文章回顾了线粒体及其蛋白质质量控制系统在动脉粥样硬化性疾病发生发展中的作用,并对该领域未来的发展前景和挑战进行展望,以期为寻找与动脉粥样硬化性疾病密切相关的特异性线粒体蛋白提供线索。     

Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

Optic atrophy 1 (OPA1)‐related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1‐related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia‐reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion, and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress. However, melatonin treatment maintained myocardial function and cardiomyocyte viability, and these effects were highly dependent on OPA1‐related mitochondrial fusion/mitophagy. At the molecular level, OPA1‐related mitochondrial fusion/mitophagy, which was normalized by melatonin, substantially rectified the excessive mitochondrial fission, promoted mitochondria energy metabolism, sustained mitochondrial function, and blocked cardiomyocyte caspase‐9‐involved mitochondrial apoptosis. However, genetic approaches with a cardiac‐specific knockout of OPA1 abolished the beneficial effects of melatonin on cardiomyocyte survival and mitochondrial homeostasis in vivo and in vitro. Furthermore, we demonstrated that melatonin affected OPA1 stabilization via the AMPK signaling pathway and that blockade of AMPK repressed OPA1 expression and compromised the cardioprotective action of melatonin. Overall, our results confirm that OPA1‐related mitochondrial fusion/mitophagy is actually modulated by melatonin in the setting of cardiac I/R injury. Moreover, manipulation of the AMPK‐OPA1‐mitochondrial fusion/mitophagy axis via melatonin may be a novel therapeutic approach to reduce cardiac I/R injury.     

线粒体相关内质网膜（MAMs）在心血管疾病中的研究进展

作为内质网和线粒体接触的结构，线粒体相关内质网膜（mitochondria-associated endoplasmic reticulum membranes，MAMs）可通过膜结构上的分子促进两种细胞器的物质和信号的交流。目前MAMs在脂质的生物合成与转运、钙稳态的维持、ROS的产生以及自噬过程中的角色逐步被证实。研究表明，MAMs在一些心血管疾病如心力衰竭、心肌缺血再灌注损伤、动脉粥样硬化的发生中十分重要。本文介绍了MAMs的分离和观察方法以及在细胞稳态维持中的作用，并讨论了MAMs在一些心血管疾病中的作用。     

A time to reap,a time to sow: Mitophagy and biogenesis in cardiac pathophysiology

Balancing mitophagy and mitochondrial biogenesis is essential for maintaining a healthy population of mitochondria and cellular homeostasis. Coordinated interplay between these two forces that govern mitochondrial turnover plays an important role as an adaptive response against various cellular stresses that can compromise cell survival. Failure to maintain the critical balance between mitophagy and mitochondrial biogenesis or homeostatic turnover of mitochondria results in a population of dysfunctional mitochondria that contribute to various disease processes. In this review we outline the mechanics and relationships between mitophagy and mitochondrial biogenesis, and discuss the implications of a disrupted balance between these two forces, with an emphasis on cardiac physiology. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".     

Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system

Mitochondria are essential organelles that produce the cellular energy source, ATP. Dysfunctional mitochondria are involved in the pathophysiology of heart disease, which is associated with reduced levels of ATP and excessive production of reactive oxygen species. Mitochondria are dynamic organelles that change their morphology through fission and fusion in order to maintain their function. Fusion connects neighboring depolarized mitochondria and mixes their contents to maintain membrane potential. In contrast, fission segregates damaged mitochondria from intact ones, where the damaged part of mitochondria is subjected to mitophagy whereas the intact part to fusion. It is generally believed that mitochondrial fusion is beneficial for the heart, especially under stress conditions, because it consolidates the mitochondria's ability to supply energy. However, both excessive fusion and insufficient fission disrupt the mitochondrial quality control mechanism and potentiate cell death. In this review, we discuss the role of mitochondrial dynamics and mitophagy in the heart and the cardiomyocytes therein, with a focus on their roles in cardiovascular disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".     

The role of mitochondria in age-related hearing loss

Age-related hearing loss (ARHL), the hearing loss associated with aging, is a vital problem in present society. The severity of hearing loss is possibly associated with the degeneration of cochlear cells. Mitochondria play a key role in the energy supply, cellular redox homeostasis, signaling, and regulation of programmed cell death. In this review, we focus on the central role of mitochondria in ARHL. The mitochondrial redox imbalance and mitochondrial DNA mutation might collaboratively involve in the process of cochlear senescence in response to the aging stress. Subsequent responses, including alteration of mitochondrial biogenesis, mitophagy, apoptosis and paraptosis, participate in the aging process from different respects.