Cited 8 time in webofscience Cited 7 time in scopus

Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson’s disease model

Title
Primary cilia mediate mitochondrial stress responses to promote dopamine neuron survival in a Parkinson’s disease model
Authors
Bae, Ji-EunKang, Gil MyungMin, Se HeeJo, Doo SinJung, Yong-KeunKim, KeetaeKim, Min-SeonCho, Dong-Hyung
DGIST Authors
Kim, Keetae
Issue Date
2019-12
Citation
Cell Death and Disease, 10(12)
Type
Article
Article Type
Article
Keywords
CELL-DEATHAUTOPHAGYCILIOGENESISMITOPHAGYDYNAMICSINJURYMTORAMPK
ISSN
2041-4889
Abstract
A primary cilium is an antenna-like structure on the cell surface that plays a crucial role in sensory perception and signal transduction. Mitochondria, the ‘powerhouse’ of the cell, control cell survival, and death. The cellular ability to remove dysfunctional mitochondria through mitophagy is important for cell survival. We show here that mitochondrial stress, caused by respiratory complex inhibitors and excessive fission, robustly stimulates ciliogenesis in different types of cells including neuronal cells. Mitochondrial stress-induced ciliogenesis is mediated by mitochondrial reactive oxygen species generation, subsequent activation of AMP-activated protein kinase and autophagy. Conversely, abrogation of ciliogenesis compromises mitochondrial stress-induced autophagy, leading to enhanced cell death. In mice, treatment with mitochondrial toxin, MPTP elicits ciliary elongation and autophagy in the substantia nigra dopamine neurons. Blockade of cilia formation in these neurons attenuates MPTP-induced autophagy but facilitates dopamine neuronal loss and motor disability. Our findings demonstrate the important role of primary cilia in cellular pro-survival responses during mitochondrial stress. © 2019, The Author(s).
URI
http://hdl.handle.net/20.500.11750/11377
DOI
10.1038/s41419-019-2184-y
Publisher
Springer Nature
Files:
Collection:
Department of New BiologyCBRG(Complex Biology Research Group)1. Journal Articles


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