Humanin is an endogenous activator of chaperone-mediated autophagy.
Humanin is an endogenous activator of chaperone-mediated autophagy.
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DOI：
10.1083/jcb.201606095
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发表时间：
2018-02-05
期刊：
影响因子：
--
通讯作者：
Muzumdar R
中科院分区：
文献类型：
--
作者：
Gong Z;Tasset I;Diaz A;Anguiano J;Tas E;Cui L;Kuliawat R;Liu H;Kühn B;Cuervo AM;Muzumdar R
Gong et al. show in multiple cell types that a mitochondrial-associate peptide, humanin, activates chaperone-mediated autophagy (CMA) by stabilizing the interaction between HSP90 and CMA substrates, thereby protecting cells from stressor-induced cell death. Chaperone-mediated autophagy (CMA) serves as quality control during stress conditions through selective degradation of cytosolic proteins in lysosomes. Humanin (HN) is a mitochondria-associated peptide that offers cytoprotective, cardioprotective, and neuroprotective effects in vivo and in vitro. In this study, we demonstrate that HN directly activates CMA by increasing substrate binding and translocation into lysosomes. The potent HN analogue HNG protects from stressor-induced cell death in fibroblasts, cardiomyoblasts, neuronal cells, and primary cardiomyocytes. The protective effects are lost in CMA-deficient cells, suggesting that they are mediated through the activation of CMA. We identified that a fraction of endogenous HN is present at the cytosolic side of the lysosomal membrane, where it interacts with heat shock protein 90 (HSP90) and stabilizes binding of this chaperone to CMA substrates as they bind to the membrane. Inhibition of HSP90 blocks the effect of HNG on substrate translocation and abolishes the cytoprotective effects. Our study provides a novel mechanism by which HN exerts its cardioprotective and neuroprotective effects.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
5.6
作者：
AUTERI, JS;OKADA, A;DICE, JF
通讯作者：
DICE, JF
DOI：
10.1016/j.bbrc.2013.08.055
发表时间：
2013-10-18
影响因子：
3.1
作者：
Klein, Laura E.;Cui, Lingguang;Gong, Zhenwei;Su, Kai;Muzumdar, Radhika
通讯作者：
Muzumdar, Radhika
影响因子：
5.3
作者：
Bandyopadhyay, Urmi;Kaushik, Susmita;Cuervo, Ana Maria
通讯作者：
Cuervo, Ana Maria
影响因子：
11.4
作者：
Cuervo, AM;Mann, L;Dice, JF
通讯作者：
Dice, JF