@article{f594ce3c3a9242e7b8435811dc1d0173,
title = "Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration",
abstract = "Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD accumulation in glia prior to or at the onset of neurodegeneration. The accumulated lipids are peroxidated in the presence of ROS. Reducing LD accumulation in glia and lipid peroxidation via targeted lipase overexpression and/or lowering ROS significantly delays the onset of neurodegeneration. Furthermore, a similar pathway leads to glial LD accumulation in Ndufs4 mutant mice with neuronal mitochondrial defects, suggesting that LD accumulation following mitochondrial dysfunction is an evolutionarily conserved phenomenon, and represents an early, transient indicator and promoter of neurodegenerative disease.",
author = "Lucy Liu and Ke Zhang and Hector Sandoval and Shinya Yamamoto and Manish Jaiswal and Elisenda Sanz and Zhihong Li and Jessica Hui and Graham, {Brett H.} and Albert Quintana and Bellen, {Hugo J.}",
note = "Funding Information: We thank Karen Schulze, Richard Palmiter, Bertrand Mollereau, and Kartik Venkatachalam for comments; Robert Rawson (SREBP antibody), Ronald K{\"u}hnlein (UAS-bmm), the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi center, and the TRiP at Harvard Medical School (NIH/NIGMS R01- GM084947) for providing stocks and reagents; Ching-On Wong for help with westerns; and Lita Duraine for TEM. Confocal microscopy was supported by the BCM Intellectual and Developmental Disabilities Research Center (NIH/NICHHD P30 HD024064). H.S. was supported by NIH 5R01GM067858, NIH T32 NS043124-11 and the Research Education and Career Horizon Institutional Research and Academic Career Development Award Fellowship 5K12GM084897. L.L. was supported by the Neuroscience graduate program training grant (5T32GM008507-18) from 2011 to 2012. S.Y. is supported by the Jan and Dan Duncan Neurological Research Institute at Texas Children{\textquoteright}s Hospital. We acknowledge support of the NW Mitochondrial Research Guild to A.Q. We acknowledge support of the NIH (1RC4GM096355), the Robert A. and Renee E. Belfer Family Foundation, the Huffington Foundation and Target ALS to H.J.B. S.Y. is supported by the Jan and Dan Duncan Neurological Research Institute at Texas Children{\textquoteright}s Hospital. H.J.B. is an Investigator of the Howard Hughes Medical Institute. ",
year = "2015",
month = jan,
day = "15",
doi = "10.1016/j.cell.2014.12.019",
language = "English (US)",
volume = "160",
pages = "177--190",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1-2",
}