Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1

@article{Ehses2009RegulationOO,
  title={Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1},
  author={Sarah Ehses and I. Raschke and G. Mancuso and Andrea Bernacchia and S. Geimer and Daniel Tondera and J. Martinou and B. Westermann and E. Rugarli and T. Langer},
  journal={The Journal of Cell Biology},
  year={2009},
  volume={187},
  pages={1023 - 1036}
}
m-AAA proteases cleave OPA1 to ensure a balance of long and short OPA1 isoforms, whereas cleavage by OMA1 causes an accumulation of the short OPA1 variants. (See also companion paper from Head et al. in this issue.) 
The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission
OPA1 processing by YEM1L and OMA1 is dispensable for mitochondrial fusion and instead drives mitochondrial fragmentation, which is crucial for mitochondrial integrity and quality control.
Fluorescence-Based Assay For Measuring OMA1 Activity.
TLDR
This chapter provides additional insight into the OMA1 activity assay, a fluorescence-based reporter assay that utilizes an eight amino acid peptide sequence referred to as the S1 cleavage site where Oma1 cleaves within OPA1 and is flanked by a fluorophore and quencher. Expand
Membrane depolarization activates the mitochondrial protease OMA1 by stimulating self‐cleavage
TLDR
It is shown that OMA1 is cleaved to a short form (S‐OMA1) by itself upon mitochondrial membrane depolarization; S‐ OMA1 is degraded quickly but could be stabilized by CCCP treatment or Prohibitin knockdown in cells. Expand
Stoichiometric expression of mtHsp40 and mtHsp70 modulates mitochondrial morphology and cristae structure via Opa1L cleavage
Imbalance between mtHsp40 and mtHsp70 enhances Opa1L cleavage, leading to cristae remodeling and eventual mitochondrial fragmentation and defective OXPHOS. This is important for understandingExpand
Mitochondrial Function: OMA1 and OPA1, the Grandmasters of Mitochondrial Health
Two new studies have identified a key protease responsible for sensing mitochondrial dysfunction, leading to the inactivation of the fusion GTPase OPA1. These studies have broad implications inExpand
YME1L controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation
Loss-of-function studies show that the human mitochondrial YME1L protease ensures cell proliferation, maintains normal cristae morphology and complex I activity, acts in an antiapoptotic manner,Expand
m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics
TLDR
AFG3L2 and YME1L1 coordinately regulate OMA1 maturation and consequently, mitochondrial dynamics, adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena. Expand
Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
TLDR
It is found that the long-form of OpA1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release, however, stoichiometric levels of the processed, short form of Opa1 (s-OPa1) work together with l-OPA1 to mediate efficient and fast membrane pore opening. Expand
Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
TLDR
It is found that the long-form of OpA1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release, however, stoichiometric levels of the processed, short form of Opa1 (s-OPa1) work together with l-OPA1 to mediate efficient and fast membrane pore opening. Expand
Processing of the dynamin Msp1p in S. pombe reveals an evolutionary switch between its orthologs Mgm1p in S. cerevisiae and OPA1 in mammals
TLDR
Results reveal that Msp1p processing may represent an evolutionary switch between Mgm1p and OPA1, and the generation of the short isoform of MSP1p neither results from the maturation of the long isoform nor correlates with mitochondrial ATP levels. Expand
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