Format

Send to

Choose Destination
Cell. 2015 Jan 15;160(1-2):177-90. doi: 10.1016/j.cell.2014.12.019.

Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration.

Author information

1
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
2
Structural and Computational Biology & Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
5
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
6
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
7
Center for Developmental Therapeutics, University of Washington, Seattle, WA, 98195, USA.
8
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Center for Developmental Therapeutics, University of Washington, Seattle, WA, 98195, USA; Department of Pediatrics, University of Washington, Seattle, WA, 98195, USA.
9
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Structural and Computational Biology & Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hbellen@bcm.edu.

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.

PMID:
25594180
PMCID:
PMC4377295
DOI:
10.1016/j.cell.2014.12.019
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center