期刊
MOLECULAR CELL
卷 69, 期 5, 页码 744-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.01.026
关键词
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资金
- Stanford Cell Science Imaging EM Facility [1S10RR026780-01]
- Department of Defense [PR150380, W81XWH-17-1-0249]
- Alfred P. Sloan Foundation
- Klingenstein Foundation
- Shurl and Kay Curci Foundation
- Marie Curie Career Integration Grant
- Junior Group Leader Fellowship of the Bonfor-Program at the University Hospital Bonn
- National Science Foundation
- Postdoctoral Research Abroad Program of the National Science Council, Taiwan
- Mayo Clinic Neuroscience Focused Research Team
- Mayo Clinic Center for Regenerative Medicine
- Michael J. Fox Foundation
- NIH/NINDS [R01 NS078086]
- Sol Goldman Charitable Trust
- Morris K. Udall PD Research Center of Excellence (NINDS) [NS072187]
- Michael J. Fox Foundation for Parkinson's Research
- Abbvie
- Avid
- Biogen
- Bristol-Myers Squibb
- Covance
- GE Healthcare
- Genentech
- GlaxoSmithKline
- Lilly
- Lundbeck
- Merck
- Meso Scale Discovery
- Pfizer
- Piramal
- Roche
- Servier
- UCB
Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure and ATP levels of PINK1-null flies and remarkably rescues their behavioral defects and dopaminergic neurodegeneration. In an extension to human relevance, we discover that the PINK1-MIC60 pathway is conserved in human neurons, and expression of several MIC60 coding variants in the mitochondrial targeting sequence found in PD patients in Drosophila impairs crista junction formation and causes locomotion deficits. These findings highlight the importance of maintenance and plasticity of crista junctions to cellular homeostasis in vivo.
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