PMID- 25038566
OWN - NLM
STAT- MEDLINE
DCOM- 20150529
LR  - 20211021
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Print)
IS  - 0300-9084 (Linking)
VI  - 105
DP  - 2014 Oct
TI  - Bound cardiolipin is essential for cytochrome c oxidase proton translocation.
PG  - 159-64
LID - S0300-9084(14)00183-7 [pii]
LID - 10.1016/j.biochi.2014.07.005 [doi]
AB  - The proton pumping activity of bovine heart cytochrome c oxidase (CcO) is 
      completely inhibited when all of the cardiolipin (CL) is removed from the enzyme 
      to produce monomeric CcO containing only 11 subunits. Only dimeric enzyme 
      containing all 13 subunits and 2-4 cardiolipin per CcO monomer exhibits a 
      "normal" proton translocating stoichiometry of  approximately 1.0 H(+) per/e(-) when 
      reconstituted into phospholipid vesicles. These fully active proteoliposomes have 
      high respiratory control ratios (RCR = 7-15) with 75-85% of the CcO oriented with 
      the cytochrome c binding sites exposed to the external medium. In contrast, 
      reconstitution of CL-free CcO results in low respiratory control ratios (RCR < 5) 
      with the enzyme randomly oriented in the vesicles, i.e.,  approximately 50 percent oriented 
      with the cytochrome c binding site exposed on the outside of the vesicle. 
      Addition of exogenous CL to the CL-free enzyme completely restores electron 
      transport activity, but restoration of proton pumping activity does not occur. 
      This is true whether CL is added to CL-free CcO prior to reconstitution into 
      phospholipid vesicles, or whether CL is included in the phospholipid mixture that 
      is used to form the vesicles. Another consequence of CL removal is the inability 
      of the 11-subunit, CL-free enzyme to dimerize upon exposure to either cholate or 
      the cholate/PC/PE/CL mixture used during proteoliposome formation (monomeric, 
      13-subunit, CL-containing CcO completely dimerizes under these conditions). 
      Therefore, a major difference between reconstitution of CL-free and CL-containing 
      CcO is the incorporation of monomeric, rather than dimeric CcO into the vesicles. 
      We conclude that bound CL is necessary for proper insertion of CcO into 
      phospholipid vesicles and normal proton translocation.
CI  - Copyright (c) 2014 Elsevier Masson SAS. All rights reserved.
FAU - Musatov, Andrej
AU  - Musatov A
AD  - Department of Biochemistry, The University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Drive, TX 78229-3900, USA. Electronic address: 
      musatov@saske.sk.
FAU - Robinson, Neal C
AU  - Robinson NC
AD  - Department of Biochemistry, The University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Drive, TX 78229-3900, USA. Electronic address: 
      robinson@uthscsa.edu.
LA  - eng
GR  - R01 GM024795/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140716
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Cardiolipins)
RN  - 0 (Liposomes)
RN  - 0 (Phospholipids)
RN  - 0 (Proton Pumps)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cardiolipins/chemistry/*metabolism
MH  - Cattle
MH  - Dimerization
MH  - Electron Transport Complex IV/antagonists & inhibitors/chemistry/*metabolism
MH  - Hydrolysis
MH  - Kinetics
MH  - Liposomes/chemistry/*metabolism
MH  - Myocardium/*metabolism/pathology
MH  - Phospholipids/metabolism
MH  - Proton Pumps/chemistry/metabolism
PMC - PMC4163530
MID - NIHMS614156
OTO - NOTNLM
OT  - Cardiolipin
OT  - Cytochrome c oxidase
OT  - Liposomes
OT  - Proton pumping
EDAT- 2014/07/20 06:00
MHDA- 2015/05/30 06:00
PMCR- 2015/10/01
CRDT- 2014/07/20 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2014/07/07 00:00 [accepted]
PHST- 2014/07/20 06:00 [entrez]
PHST- 2014/07/20 06:00 [pubmed]
PHST- 2015/05/30 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - S0300-9084(14)00183-7 [pii]
AID - 10.1016/j.biochi.2014.07.005 [doi]
PST - ppublish
SO  - Biochimie. 2014 Oct;105:159-64. doi: 10.1016/j.biochi.2014.07.005. Epub 2014 Jul 
      16.