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

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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Bae JE,Kang GM,Min SH,Jo DS,Jung YK,Kim K,Kim MS,Cho DH

doi

10.1038/s41419-019-2184-y

subject

Has Abstract

pub_date

2019-12-16 00:00:00

pages

952

issue

12

issn

2041-4889

pii

10.1038/s41419-019-2184-y

journal_volume

10

pub_type

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