Direct Membrane Association Drives Mitochondrial Fission by the Parkinson Disease-associated Protein α-Synuclein
Gladstone Institutes · University of California, San Francisco · +6 more institutions
Abstract
The protein α-synuclein has a central role in Parkinson disease, but the mechanism by which it contributes to neural degeneration remains unknown. We now show that the expression of α-synuclein in mammalian cells, including neurons in vitro and in vivo, causes the fragmentation of mitochondria. The effect is specific for synuclein, with more fragmentation by α- than β- or γ-isoforms, and it is not accompanied by changes in the morphology of other organelles or in mitochondrial membrane potential. However, mitochondrial fragmentation is eventually followed by a decline in respiration and neuronal death. The fragmentation does not require the mitochondrial fission protein Drp1 and involves a direct interaction…
Citation impact
- FWCI
- 27.05
- Percentile
- 100%
- References
- 103
Authors
16- KNKen Nakamura
Gladstone Institutes, University of California, San Francisco
- VMVenu M. Nemani
Johns Hopkins University, University of California, San Francisco, Johns Hopkins Medicine
- FAFarnaz Azarbal
Johns Hopkins University, University of California, San Francisco, Johns Hopkins Medicine
- GSGaia Skibinski
Gladstone Institutes, Taube Koret Center
- JMJon M. Levy
Johns Hopkins University, University of California, San Francisco, Johns Hopkins Medicine
Topics & keywords
- Cardiolipin
- Mitochondrial fission
- Mitochondrion
- Cell biology
- Fragmentation (computing)
- Biology
- Synuclein
- mitochondrial fusion
- Good health and well-being
Funding
- LLLarry L. Hillblom Foundation
- MFMcKnight Foundation
- GIGladstone Institutes
- NINational Institutes of HealthAwards: NS057096, AG18440, AG022074, DA10154, GM089853
- NINational Institute on AgingAward: AG18440
- NINational Institute on Drug AbuseAward: DA10154
- NINational Institute of Neurological Disorders and StrokeAward: NS057096