Mitochondrial and cellular mechanisms for managing lipid excess.
Mitochondrial and cellular mechanisms for managing lipid excess.
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DOI：
10.3389/fphys.2014.00282
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发表时间：
2014
影响因子：
4
通讯作者：
Cortassa SC
中科院分区：
文献类型：
--
作者：
Aon MA;Bhatt N;Cortassa SC
目前的科学争论集中在脂质和线粒体功能对人类健康、营养和疾病的各个方面的影响上，其中包括脂肪毒性与骨骼肌胰岛素抵抗的发生以及肥胖和糖尿病中心脏功能障碍的关联。线粒体在衰老和流行的急性或慢性疾病中起着重要作用。脂质是线粒体的主要燃料，但这些分子也可以作为氧化磷酸化的解偶联剂和抑制剂。关于这些相互矛盾的作用的功能组成及其对线粒体细胞能量学/氧化还原状态的影响的知识是不完整的。细胞将脂肪酸（FAs）储存为三酰甘油，并将其包装成细胞质脂滴（ld）。新出现的数据表明，LD是一个高度动态的FAs存储池，可用于能量储备。脂质过度包装进入ld可以被视为一种适应性反应，以满足能量供应，而不妨碍线粒体或细胞氧化还原状态，并保持低浓度的脂毒性中间体。本文综述了肝脏、心脏和骨骼肌中线粒体在运动等相关生理条件下对脂质的作用和利用机制。我们报道了perilipins，这是一个与LDs相关的蛋白家族，它对细胞装载脂质做出反应。证据表明，除了物理接触，线粒体和ld表现出代谢相互作用提出和讨论。提出了一个线粒体通道脂质利用的假设模型。线粒体中脂质的直接传递和通道处理可能是一种可靠而有效的方法，可以将活性氧（ROS）维持在与信号传导相容的水平，同时确保稳健可靠的能量供应。
Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete. Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates. Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g., exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain reactive oxygen species (ROS) within levels compatible with signaling while ensuring robust and reliable energy supply.
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DOI：
10.1016/j.biocel.2009.02.016
发表时间：
2009-10
影响因子：
4
作者：
Aon, M. A.;Cortassa, S.;Akar, F. G.;Brown, D. A.;Zhou, L.;O'Rourke, B.
通讯作者：
O'Rourke, B.
谷胱甘肽氧化诱导的心律不齐可以通过预防线粒体去极化来抑制。
影响因子：
5
作者：
Brown, David A.;Aon, Miguel A.;Frasier, Chad R.;Sloan, Ruben C.;Maloney, Andrew H.;Anderson, Ethan J.;O'Rourke, Brian
通讯作者：
O'Rourke, Brian
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
4.8
作者：
Aon, Miguel A.;Cortassa, Sonia;O'Rourke, Brian
通讯作者：
O'Rourke, Brian
DOI：
10.1016/j.bbalip.2009.04.002
发表时间：
2009-06
影响因子：
4.8
作者：
Bickel, Perry E.;Tansey, John T.;Welte, Michael A.
通讯作者：
Welte, Michael A.