Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease

@article{Krick2008Mpv17lPA,
  title={Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease},
  author={Stefanie Krick and Shaolin Shi and Wenjun Ju and Christian Faul and Su-yi Tsai and Peter Mundel and Erwin P. B{\"o}ttinger},
  journal={Proceedings of the National Academy of Sciences},
  year={2008},
  volume={105},
  pages={14106 - 14111}
}
Cellular localization determines whether the serine protease HtrA2 exerts pro- or antiapoptotic functions. In contrast to the well-characterized proapoptotic function of cytosolic HtrA2, mechanisms underlying the mitochondrial protective role are poorly understood. Mpv17l is a transmembrane protein previously implicated in peroxisomal reactive oxygen species metabolism and a close homolog of the inner mitochondrial membrane protein Mpv17. Here we demonstrate a previously undescribed direct… Expand
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The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity
TLDR
Proteome analysis of supernatant of isolated mitochondria exposed to recombinant tBid revealed the presence of the serine protease Omi, also called HtrA2, and an interaction between endogeneous Omi and recombinant XIAP is demonstrated. Expand
Neuroprotective Role of the Reaper-Related Serine Protease HtrA2/Omi Revealed by Targeted Deletion in Mice
TLDR
Mammalian HtrA2/Omi is likely to function in vivo in a manner similar to that of its bacterial homologues DegS and DegP, which are involved in protection against cell stress, and not like the proapoptotic Reaper family proteins in Drosophila melanogaster. Expand
Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase Interaction*
TLDR
The results provide clear evidence for the involvement of a mitochondrial serine protease in the apoptotic pathway, emphasizing the critical role of the mitochondria in cell death. Expand
HtrA2 Promotes Cell Death through Its Serine Protease Activity and Its Ability to Antagonize Inhibitor of Apoptosis Proteins*
TLDR
HtrA2 can, like DIABLO/Smac, prevent XIAP inhibition of active caspase 3in vitro and is able to counteract XIAP protection of mammalian NT2 cells against UV-induced cell death. Expand
Binding Specificity and Regulation of the Serine Protease and PDZ Domains of HtrA2/Omi*
TLDR
Unexpectedly, binding of X-linked inhibitor of apoptosis protein (XIAP) to the Reaper motif of HtrA2/Omi results in a marked increase in proteolytic activity, suggesting a new role for IAPs. Expand
Hax1-mediated processing of HtrA2 by Parl allows survival of lymphocytes and neurons
TLDR
A previously unknown sequence of interactions involving a Bcl-2-family-related protein and mitochondrial proteases in the ability to resist the induction of apoptosis when cytokines are limiting is identified. Expand
The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
TLDR
It is suggested that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress. Expand
Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis.
TLDR
These results indicate that unlike Smac/DIABLO, Omi/HtrA2's catalytic cleavage of IAPs is a key mechanism for it to irreversibly inactivate I APs and promote apoptosis. Expand
Cytochrome C Maintains Mitochondrial Transmembrane Potential and Atp Generation after Outer Mitochondrial Membrane Permeabilization during the Apoptotic Process
TLDR
It is found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30–60 min and is then maintained. Expand
Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes.
TLDR
The identification and characterization of a human homolog of the M-LP (M-LPH) gene and its participation in reactive oxygen species metabolism are reported. Expand
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