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Stress‐induced OMA 1 activation and autocatalytic turnover regulate OPA 1‐dependent mitochondrial dynamics
Author(s) -
Baker Michael J,
Lampe Philipp A,
Stojanovski Diana,
Korwitz Anne,
Anand Ruchika,
Tatsuta Takashi,
Langer Thomas
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386474
Subject(s) - biology , autocatalysis , microbiology and biotechnology , dynamics (music) , biophysics , mitochondrion , biochemistry , physics , acoustics , catalysis
The dynamic network of mitochondria fragments under stress allowing the segregation of damaged mitochondria and, in case of persistent damage, their selective removal by mitophagy. Mitochondrial fragmentation upon depolarisation of mitochondria is brought about by the degradation of central components of the mitochondrial fusion machinery. The OMA 1 peptidase mediates the degradation of long isoforms of the dynamin‐like GTP ase OPA 1 in the inner membrane. Here, we demonstrate that OMA 1‐mediated degradation of OPA 1 is a general cellular stress response. OMA 1 is constitutively active but displays strongly enhanced activity in response to various stress insults. We identify an amino terminal stress‐sensor domain of OMA 1, which is only present in homologues of higher eukaryotes and which modulates OMA 1 proteolysis and activation. OMA 1 activation is associated with its autocatalyic degradation, which initiates from both termini of OMA 1 and results in complete OMA 1 turnover. Autocatalytic proteolysis of OMA 1 ensures the reversibility of the response and allows OPA 1‐mediated mitochondrial fusion to resume upon alleviation of stress. This differentiated stress response maintains the functional integrity of mitochondria and contributes to cell survival.