期刊
CELLULAR SIGNALLING
卷 27, 期 9, 页码 1840-1849出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2015.06.001
关键词
Isc1p; Sit4p; Dnm1p; Ceramide; Mitochondrial dynamics; Mitophagy
类别
资金
- FEDER funds through the Operational Competitiveness Programme - COMPETE
- FCT - Fundacao para a Ciencia e a Tecnologia [FCOMP-01-0124-FEDER-028210 (PTDC/BBB-BQB/1850/2012), PEst-OE/BIA/UI4050/2014]
- FCT [SFRH/BD/72134/2010, SFRH/BD/48125/2008, SFRH/BPD/89980/2012]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/48125/2008, SFRH/BD/72134/2010] Funding Source: FCT
Mitochondria function as the powerhouses of the cell for energy conversion through the oxidative phosphoryladon process. Accumulation of dysfunctional mitochondria promotes a bioenergetic crisis and cell death by apoptosis. Yeast cells lacking Isc1p, an orthologue of mammalian neutral sphingomyelinase type 2, exhibit mitochondrial dysfunction and shortened lifespan associated with the accumulation of specific ceramide species and activation of the PP2A-like protein phosphatase Sit4p and of the Hog1p kinase. Here, we show that isc1 Delta cells display hyperactivation of mitophagy that is suppressed by downregulating Sit4p, Hog1p or the TORC1-Sch9p pathway. Notably, isc1 Delta cells also have high levels of Dnm1p associated with unbalanced mitochondrial fission, leading to mitochondrial fragmentation, and DNM1 deletion suppressed the oxidative stress sensitivity and shortened lifespan of isc1 Delta cells. Moreover, Isc1p and Dnm1p physically interact, suggesting a possible regulatory role for Isc1p in mitochondrial dynamics. Overall, outwork demonstrates that Isc1p-mediated ceramide signalling regulates mitophagy and mitochondrial dynamics in yeast with impact on mitochondrial function and lifespan. Since ceramides have been implicated in ageing and diseases associated with mitochondrial dysfunction, our findings suggest that therapeutic strategies targeting ceramide signalling may improve mitochondrial function and human healthspan. (C) 2015 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据