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PMID:16839884

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Citation

Cipolat, S, Rudka, T, Hartmann, D, Costa, V, Serneels, L, Craessaerts, K, Metzger, K, Frezza, C, Annaert, W, D'Adamio, L, Derks, C, Dejaegere, T, Pellegrini, L, D'Hooge, R, Scorrano, L and De Strooper, B (2006) Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 126:163-75

Abstract

Rhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. Presenilin-associated rhomboid-like (PARL) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. Parl-/- mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic atrophy leading to cachectic death. Atrophy is sustained by increased apoptosis, both in and ex vivo. Parl-/- cells display normal mitochondrial morphology and function but are no longer protected against intrinsic apoptotic death stimuli by the dynamin-related mitochondrial protein OPA1. Parl-/- mitochondria display reduced levels of a soluble, intermembrane space (IMS) form of OPA1, and OPA1 specifically targeted to IMS complements Parl-/- cells, substantiating the importance of PARL in OPA1 processing. Parl-/- mitochondria undergo faster apoptotic cristae remodeling and cytochrome c release. These findings implicate regulated intramembrane proteolysis in controlling apoptosis.

Links

PubMed Online version:10.1016/j.cell.2006.06.021

Keywords

Animals; Apoptosis/physiology; Cachexia/genetics; Cell Line; Cells, Cultured; Cytochromes c/metabolism; Down-Regulation/genetics; Female; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; Genes, Lethal; Lymphocytes/metabolism; Lymphocytes/pathology; Metalloproteases/genetics; Metalloproteases/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria/genetics; Mitochondria/metabolism; Mitochondria/ultrastructure; Mitochondrial Membranes/metabolism; Mitochondrial Membranes/ultrastructure; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BCL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q07813

F

Seeded From UniProt

complete

MOUSE:OPA1

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:OPA1

involved_in

GO:2001243: negative regulation of intrinsic apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:Q5XJY4)

Seeded From UniProt

complete

MOUSE:OPA1

involved_in

GO:0090201: negative regulation of release of cytochrome c from mitochondria

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:Q5XJY4)|happens_during(GO:2001243)

Seeded From UniProt

complete

MOUSE:BAX

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P10417

F

Seeded From UniProt

complete

MOUSE:PARL

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PARL

involved_in

GO:2001243: negative regulation of intrinsic apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:P58281)

Seeded From UniProt

complete

MOUSE:PARL

involved_in

GO:0090201: negative regulation of release of cytochrome c from mitochondria

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_participant:(UniProtKB:P58281)|happens_during(GO:2001243)

Seeded From UniProt

complete

MOUSE:OPA1

part_of

GO:0005743: mitochondrial inner membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:OPA1

involved_in

GO:0090201: negative regulation of release of cytochrome c from mitochondria

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_participant:(UniProtKB:Q5XJY4)|happens_during(GO:2001243)

Seeded From UniProt

complete

MOUSE:OPA1

involved_in

GO:2001243: negative regulation of intrinsic apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_participant:(UniProtKB:Q5XJY4)

Seeded From UniProt

complete


See also

References

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