Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes.
Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes.
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DOI：
10.1016/j.cmet.2021.08.002
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发表时间：
2021-09-07
期刊：
影响因子：
29
通讯作者：
Scherer PE
中科院分区：
文献类型：
--
作者：
Crewe C;Funcke JB;Li S;Joffin N;Gliniak CM;Ghaben AL;An YA;Sadek HA;Gordillo R;Akgul Y;Chen S;Samovski D;Fischer-Posovszky P;Kusminski CM;Klein S;Scherer PE
脂肪细胞在肥胖症中经历强烈的能量应激，导致线粒体质量和功能丧失。我们发现脂肪细胞通过快速而有力地释放小细胞外囊泡（sEV）来应对线粒体应激。这些 sEV 含有具有呼吸能力但受到氧化损伤的线粒体颗粒，这些颗粒进入循环系统并被心肌细胞吸收，并在心肌细胞中引发ROS的爆发。结果是心脏中补偿性抗氧化信号传导，保护心肌细胞免受急性氧化应激，这与预处理范例一致。因此，单次注射来自高强度脂肪细胞的 sEV 可限制小鼠的心脏缺血/再灌注损伤。这项研究首次描述了组织间功能性线粒体转移，也是“器官间线粒体毒物兴奋作用”的第一个脊椎动物例子。因此，这些看似有毒的脂肪细胞 sEV 可能提供一种有效的心脏保护生理途径，以对抗肥胖引起的不可避免的脂毒性或缺血性应激。克鲁等人。等人。报道称，脂肪细胞释放含有受损线粒体的 sEV，以应对能量压力，例如慢性肥胖症中所见的情况。 sEV 相关线粒体会诱导心脏组织中短暂的线粒体氧化应激，从而产生抗氧化反应。脂肪细胞 sEV 从而预处理心脏以防止缺血/再灌注损伤。
Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively-damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes where they trigger a burst of ROS. The result is compensatory antioxidant signaling in the heart that protects cardiomyocytes from acute oxidative stress, consistent with a preconditioning paradigm. As such, a single injection of sEVs from energetically stressed adipocytes limits cardiac ischemia/reperfusion injury in mice. This study provides the first description of functional mitochondrial transfer between tissues and the first vertebrate example of “inter-organ mitohormesis”. Thus, these seemingly toxic adipocyte sEVs may provide a physiological avenue of potent cardio-protection against the inevitable lipotoxic or ischemic stresses elicited by obesity. Crewe et. al. report that adipocytes release sEVs containing damaged mitochondria in response to energetic stress, such as that seen in chronic obesity. The sEV-associated mitochondria induce transient mitochondrial oxidative stress in cardiac tissue, resulting in an antioxidant response. Adipocyte sEVs thereby precondition the heart to protect against ischemia/reperfusion injury.
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DOI：
10.1007/s00018-018-2773-4
发表时间：
2018-08
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Karimi N;Cvjetkovic A;Jang SC;Crescitelli R;Hosseinpour Feizi MA;Nieuwland R;Lötvall J;Lässer C
通讯作者：
Lässer C
影响因子：
7.7
作者：
Curtis JM;Grimsrud PA;Wright WS;Xu X;Foncea RE;Graham DW;Brestoff JR;Wiczer BM;Ilkayeva O;Cianflone K;Muoio DE;Arriaga EA;Bernlohr DA
通讯作者：
Bernlohr DA
影响因子：
20.1
作者：
Ackers-Johnson M;Li PY;Holmes AP;O'Brien SM;Pavlovic D;Foo RS
通讯作者：
Foo RS
影响因子：
20.8
作者：
An, Yu A.;Crewe, Clair;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.
影响因子：
37.8
作者：
Gan, Lu;Xie, Dina;Wang, Yajing
通讯作者：
Wang, Yajing