PMID- 27998984
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20210314
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 292
IP  - 5
DP  - 2017 Feb 3
TI  - The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase 
      Assembly.
PG  - 1815-1825
LID - S0021-9258(20)36710-7 [pii]
LID - 10.1074/jbc.M116.766980 [doi]
AB  - Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory 
      enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several 
      enzymes, including the evolutionarily conserved heme a synthase (Cox15). 
      Oligomerization of Cox15 appears to be important for the process of heme a 
      biosynthesis and transfer to maturing CcO. However, the details of this process 
      remain elusive, and the roles of any additional CcO assembly factors that may be 
      involved remain unclear. Here we report the systematic analysis of one such 
      uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces 
      cerevisiae that this evolutionarily conserved protein is necessary for Cox15 
      oligomerization and function. Pet117 is shown to reside in the mitochondrial 
      matrix, where it is associated with the inner membrane. Pet117 functions at the 
      later maturation stages of the core CcO subunit Cox1 that precede Cox1 
      hemylation. Pet117 also physically interacts with Cox15 and specifically mediates 
      the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction 
      observed by co-immunoprecipitation persists in the absence of heme a synthase 
      activity, is dependent upon Cox1 synthesis and early maturation steps, and is 
      further dependent upon the presence of the matrix-exposed, unstructured linker 
      region of Cox15 needed for Cox15 oligomerization, suggesting that this region 
      mediates the interaction or that the interaction is lost when Cox15 is unable to 
      oligomerize. Based on these findings, it was concluded that Pet117 mediates 
      coupling of heme a synthesis to the CcO assembly process in eukaryotes.
CI  - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Taylor, Nicholas G
AU  - Taylor NG
AD  - From the Department of Chemistry and Biochemistry, College of Charleston, 
      Charleston, South Carolina 29424.
FAU - Swenson, Samantha
AU  - Swenson S
AD  - the Department of Biochemistry and Nebraska Redox Biology Center, University of 
      Nebraska, Lincoln, Nebraska 68588.
FAU - Harris, Nicholas J
AU  - Harris NJ
AD  - From the Department of Chemistry and Biochemistry, College of Charleston, 
      Charleston, South Carolina 29424.
FAU - Germany, Edward M
AU  - Germany EM
AD  - the Department of Biochemistry and Nebraska Redox Biology Center, University of 
      Nebraska, Lincoln, Nebraska 68588.
FAU - Fox, Jennifer L
AU  - Fox JL
AD  - From the Department of Chemistry and Biochemistry, College of Charleston, 
      Charleston, South Carolina 29424. Electronic address: foxjl@cofc.edu.
FAU - Khalimonchuk, Oleh
AU  - Khalimonchuk O
AD  - the Department of Biochemistry and Nebraska Redox Biology Center, University of 
      Nebraska, Lincoln, Nebraska 68588. Electronic address: okhalimonchuk2@unl.edu.
LA  - eng
GR  - P20 GM103499/GM/NIGMS NIH HHS/United States
GR  - R01 GM108975/GM/NIGMS NIH HHS/United States
GR  - P20 RR016461/RR/NCRR NIH HHS/United States
GR  - U54 DK110858/DK/NIDDK NIH HHS/United States
GR  - P30 GM103335/GM/NIGMS NIH HHS/United States
GR  - T32 GM107001/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20161220
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (COX15 protein, S cerevisiae)
RN  - 0 (Membrane Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 1.9.3.1 (Cox1 protein, S cerevisiae)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 4.99.1.1 (Ferrochelatase)
SB  - IM
MH  - Electron Transport Complex IV/genetics/*metabolism
MH  - Ferrochelatase/genetics/*metabolism
MH  - Membrane Proteins/genetics/*metabolism
MH  - Protein Multimerization/*physiology
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
PMC - PMC5290955
OTO - NOTNLM
OT  - Cox15
OT  - Pet117
OT  - cytochrome c oxidase (Complex IV)
OT  - heme
OT  - mitochondria
OT  - mitochondrial disease
OT  - oligomerization
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2016/12/22 06:00
MHDA- 2017/06/02 06:00
PMCR- 2018/02/03
CRDT- 2016/12/22 06:00
PHST- 2016/11/08 00:00 [received]
PHST- 2016/12/13 00:00 [revised]
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
PHST- 2016/12/22 06:00 [entrez]
PHST- 2018/02/03 00:00 [pmc-release]
AID - S0021-9258(20)36710-7 [pii]
AID - M116.766980 [pii]
AID - 10.1074/jbc.M116.766980 [doi]
PST - ppublish
SO  - J Biol Chem. 2017 Feb 3;292(5):1815-1825. doi: 10.1074/jbc.M116.766980. Epub 2016 
      Dec 20.