English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria

MPS-Authors
/persons/resource/persons281120

Sprenger,  H.-G.
Department Langer - Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278030

Langer,  T.
Department Langer - Mitochondrial Proteostasis, Max Planck Institute for Biology of Ageing, Max Planck Society;

External Resource
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Korwitz, A., Merkwirth, C., Richter-Dennerlein, R., Troder, S. E., Sprenger, H.-G., Quiros, P. M., et al. (2016). Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria. J Cell Biol, 212(2), 157-66. doi:10.1083/jcb.201507022.


Cite as: https://hdl.handle.net/21.11116/0000-000B-7187-D
Abstract
Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondrial morphology under stress and in disease. Stress-induced OPA1 processing by OMA1 triggersmitochondrial fragmentation, which is associated with mitophagy and apoptosis in vitro. Here, we identify OMA1 as a critical regulator of neuronal survival in vivo and demonstrate that stress-induced OPA1 processing by OMA1 promotes neuronal death and neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds as a model of neurodegeneration, we demonstrate that additional ablation of Oma1 delays neuronal loss and prolongs lifespan. This is accompanied by the accumulation of fusion-active, long OPA1 forms, which stabilize the mitochondrial genome but do not preserve mitochondrial cristae or respiratory chain supercomplex assembly in prohibitin-depleted neurons. Thus, long OPA1 forms can promote neuronal survival independently of cristae shape, whereas stress-induced OMA1 activation and OPA1 cleavage limit mitochondrial fusion and promote neuronal death.