Journal article
The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective
Cell reports (Cambridge), Vol.16(9), pp.2399-2414
08/30/2016
DOI: 10.1016/j.celrep.2016.07.077
PMID: 27545884
Abstract
Immunological mediators that originate outside the nervous system can affect neuronal health. However, their roles in neurodegeneration remain largely unknown. Here, we show that the p38MAPK-mediated immune pathway activated in intestinal cells of Caenorhabditis elegans upon mitochondrial dysfunction protects neurons in a cell-non-autonomous fashion. Specifically, mitochondrial complex I dysfunction induced by rotenone activates the p38MAPK/CREB/ATF-7-dependent innate immune response pathway in intestinal cells of C. elegans. Activation of p38MAPK in the gut is neuroprotective. Enhancing the p38MAPK-mediated immune pathway in intestinal cells alone suppresses rotenone-induced dopaminergic neuron loss, while downregulating it in the intestine exacerbates neurodegeneration. The p38MAPK/ATF-7 immune pathway modulates autophagy and requires autophagy and the PTEN-induced putative kinase PINK-1 for conferring neuroprotection. Thus, mitochondrial damage induces the clearance of mitochondria by the immune pathway, protecting the organism from the toxic effects of mitochondrial dysfunction. We propose that mitochondria are subject to constant surveillance by innate immune mechanisms.
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•Rotenone exposure activates the p38MAPK/ATF-7 immune pathway in the C. elegans gut•The p38MAPK/ATF-7 immune pathway is triggered by mitochondrial complex I dysfunction•p38MAPK/ATF-7 activity in the gut protects from rotenone-induced neurodegeneration•Neuroprotection through p38MAPK/ATF-7 activation occurs through mitophagy
Chikka et al. find that mitochondrial complex I damage activates the p38MAPK/ATF-7 signaling pathway in the intestine of C. elegans. Activation of the p38MAPK/ATF-7 immune pathway in the intestine is neuroprotective and sufficient to prevent rotenone-induced degeneration of dopaminergic neurons.
Details
- Title: Subtitle
- The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective
- Creators
- Madhusudana Rao Chikka - Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USACharumathi Anbalagan - Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USAKatherine Dvorak - Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USAKyle Dombeck - Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USAVeena Prahlad - Department of Biology, Aging Mind and Brain Initiative, 143 Biology Building East, 338 BBE, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.16(9), pp.2399-2414
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.celrep.2016.07.077
- PMID
- 27545884
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Language
- English
- Date published
- 08/30/2016
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9983992087802771
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