PMID- 18076378
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20220223
IS  - 1768-322X (Electronic)
IS  - 0248-4900 (Linking)
VI  - 100
IP  - 5
DP  - 2008 May
TI  - Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial 
      membrane potential.
PG  - 315-25
AB  - BACKGROUND INFORMATION: Human OPA1 (optic atrophy type 1) is a dynamin-related 
      protein of the mitochondrial IMS (intermembrane space) involved in membrane 
      fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in 
      two isoforms generated by the serine protease Pcp1p/Rbd1p, OPA1 exists in various 
      isoforms generated by alternative splicing and processing. In the present paper, 
      we focus on protease processing of OPA1. RESULTS: We find that various mammalian 
      cell types display a similar pattern of OPA1 isoforms [two L-OPA1 (long isoforms 
      of OPA1) and three S-OPA1 (short isoforms of OPA1)] and that loss of the inner 
      membrane potential, but not inhibition of oxidative phosphorylation or 
      glycolysis, induces rapid and complete processing of L-OPA1 to S-OPA1. In 
      isolated mitochondria, OPA1 processing was inhibited by heavy-metal chelators, 
      pointing to processing by a mitochondrial metalloprotease. The pattern of OPA1 
      isoforms and its processing kinetics were normal in mitochondria devoid of the 
      serine protease PARL (presenilins-associated rhomboid-like protein) - the human 
      orthologue of Pcp1/Rbd1 - and in cells from patients carrying homozygous 
      mutations in SPG7 (spastic paraplegia type 7), a gene encoding the 
      matrix-oriented metalloprotease paraplegin. In contrast, OPA1 processing kinetics 
      were delayed upon knock-down of YME1L (human yme1-like protein), an IMS-oriented 
      metalloprotease. OPA1 processing was also stimulated during apoptosis, but 
      inhibition of this processing did not affect apoptotic release of OPA1 and 
      cytochrome c. Finally, we show that all OPA1 isoforms interact with Mfn1 
      (mitofusin 1) and Mfn2 and that these interactions are not affected by 
      dissipation of DeltaPsim (inner mitochondrial membrane potential) or OPA1 
      processing. CONCLUSIONS: Metalloprotease-mediated processing of OPA1 is modulated 
      by the inner membrane potential and is likely to be mediated by the YME1L 
      protease.
FAU - Guillery, Olwenn
AU  - Guillery O
AD  - Inserm U582, 75651 Paris cedex 13, France.
FAU - Malka, Florence
AU  - Malka F
FAU - Landes, Thomas
AU  - Landes T
FAU - Guillou, Emmanuelle
AU  - Guillou E
FAU - Blackstone, Craig
AU  - Blackstone C
FAU - Lombes, Anne
AU  - Lombes A
FAU - Belenguer, Pascale
AU  - Belenguer P
FAU - Arnoult, Damien
AU  - Arnoult D
FAU - Rojo, Manuel
AU  - Rojo M
LA  - eng
SI  - GENBANK/NM015560
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biol Cell
JT  - Biology of the cell
JID - 8108529
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Protein Isoforms)
RN  - EC 3.4.- (Metalloproteases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (YME1L1 protein, human)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (MFN2 protein, human)
RN  - EC 3.6.1.- (OPA1 protein, human)
RN  - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
RN  - EC 3.6.5.- (Mfn1 protein, human)
SB  - IM
MH  - ATPases Associated with Diverse Cellular Activities
MH  - GTP Phosphohydrolases/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Potential, Mitochondrial/*physiology
MH  - Membrane Proteins/metabolism
MH  - Membrane Transport Proteins/metabolism
MH  - Metalloendopeptidases/*metabolism
MH  - Metalloproteases/*metabolism
MH  - Mitochondrial Membrane Transport Proteins
MH  - Mitochondrial Membranes/*enzymology
MH  - Mitochondrial Proteins/metabolism
MH  - Molecular Sequence Data
MH  - Protein Isoforms/metabolism
MH  - Protein Processing, Post-Translational
MH  - RNA Interference/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2007/12/14 09:00
MHDA- 2008/08/14 09:00
CRDT- 2007/12/14 09:00
PHST- 2007/12/14 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2007/12/14 09:00 [entrez]
AID - BC20070110 [pii]
AID - 10.1042/BC20070110 [doi]
PST - ppublish
SO  - Biol Cell. 2008 May;100(5):315-25. doi: 10.1042/BC20070110.