Pryde, KR;
Taanman, JW;
Schapira, AH;
(2016)
A LON-ClpP Proteolytic Axis Degrades Complex I to Extinguish ROS Production in Depolarized Mitochondria.
CELL REPORTS
, 17
(10)
pp. 2522-2531.
10.1016/j.celrep.2016.11.027.
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Abstract
Mitochondrial dysfunction is implicated in numerous neurodegenerative disorders and in Parkinson’s disease (PD) in particular. PINK1 and Parkin gene mutations are causes of autosomal recessive PD, and these respective proteins function cooperatively to degrade depolarized mitochondria (mitophagy). It is widely assumed that impaired mitophagy causes PD, as toxic reactive oxygen species (ROS)-producing mitochondria accumulate and progressively drive neurodegeneration. Instead, we report that a LON-ClpP proteolytic quality control axis extinguishes ROS in depolarized mitochondria by degrading the complex I ROS-generating domain. Complex I deficiency has also been identified in PD brain, and our study provides a compelling non-genetic mechanistic rationale to explain this observation: intact complex I depletes if mitochondrial bioenergetic capacity is robustly attenuated.
| Type: | Article |
|---|---|
| Title: | A LON-ClpP Proteolytic Axis Degrades Complex I to Extinguish ROS Production in Depolarized Mitochondria |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2016.11.027 |
| Publisher version: | http://dx.doi.org/10.1016/j.celrep.2016.11.027 |
| Language: | English |
| Additional information: | © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, NADH-UBIQUINONE REDUCTASE, PARKINSONS-DISEASE, PROTEIN, TRANSITION, MUTATIONS, ATP, NEURONS, PINK1, DEFICIENCY, MECHANISM, mitophagy; NADH:ubiquinone oxidoreductase; complex I; mitochondrial proteases; ClpP; LON; mitochondria; retrograde signaling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1534321 |
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