GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20038678

From GONUTS
Jump to: navigation, search
Citation

Ehses, S, Raschke, I, Mancuso, G, Bernacchia, A, Geimer, S, Tondera, D, Martinou, JC, Westermann, B, Rugarli, EI and Langer, T (2009) Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J. Cell Biol. 187:1023-36

Abstract

Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1, whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria induces OPA1 processing and results in mitochondrial fragmentation, allowing the selective removal of damaged mitochondria. In this study, we demonstrate that two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities [m-AAA]) protease, variable assemblies of the conserved subunits paraplegin, AFG3L1 and -2, and the ATP-independent peptidase OMA1. Functionally redundant isoenzymes of the m-AAA protease ensure the balanced accumulation of long and short isoforms of OPA1 required for mitochondrial fusion. The loss of AFG3L2 in mouse tissues, down-regulation of AFG3L1 and -2 in mouse embryonic fibroblasts, or the expression of a dominant-negative AFG3L2 variant in human cells decreases the stability of long OPA1 isoforms and induces OPA1 processing by OMA1. Moreover, cleavage by OMA1 causes the accumulation of short OPA1 variants if mitochondrial DNA is depleted or mitochondrial activities are impaired. Our findings link distinct peptidases to constitutive and induced OPA1 processing and shed new light on the pathogenesis of neurodegenerative disorders associated with mutations in m-AAA protease subunits.

Links

PubMed PMC2806285 Online version:10.1083/jcb.200906084

Keywords

ATP-Dependent Proteases; Adenosine Triphosphatases/metabolism; Animals; Cells, Cultured; Enzyme Stability; GTP Phosphohydrolases/genetics; GTP Phosphohydrolases/metabolism; Humans; Isoenzymes/genetics; Isoenzymes/metabolism; Isoenzymes/physiology; Metalloendopeptidases/genetics; Metalloendopeptidases/metabolism; Metalloendopeptidases/physiology; Metalloproteases/genetics; Metalloproteases/metabolism; Metalloproteases/physiology; Mice; Mitochondria/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Mitochondrial Proteins/physiology; RNA Interference

Significance

Annotations

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

MOUSE:AFG32

acts_upstream_of_or_within

GO:0008053: mitochondrial fusion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928277

P

Seeded From UniProt

complete

MOUSE:AFG32

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG32

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914263
MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG32

acts_upstream_of_or_within

GO:0042407: cristae formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG32

acts_upstream_of_or_within

GO:0042407: cristae formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914263
MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG32

acts_upstream_of_or_within

GO:0034982: mitochondrial protein processing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928277

P

Seeded From UniProt

complete

MOUSE:DNM1L

acts_upstream_of_or_within

GO:0000266: mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0008053: mitochondrial fusion

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914263
MGI:MGI:1916847

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0042407: cristae formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0042407: cristae formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914263
MGI:MGI:1916847

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:AFG31

acts_upstream_of_or_within

GO:0034982: mitochondrial protein processing

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847

P

Seeded From UniProt

complete

MOUSE:OMA1

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847
MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:OMA1

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000057)

Seeded From UniProt

complete

MOUSE:OMA1

acts_upstream_of_or_within

GO:0042407: cristae formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1916847
MGI:MGI:1928277

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:OMA1

acts_upstream_of_or_within

GO:0034982: mitochondrial protein processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DNM1L

acts_upstream_of_or_within

GO:0000266: mitochondrial fission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:OPA1

acts_upstream_of_or_within

GO:0008053: mitochondrial fusion

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:OPA1

acts_upstream_of_or_within

GO:0007005: mitochondrion organization

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0000057)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.