PMID- 35053273
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220716
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jan 13
TI  - The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c 
      Oxidase.
LID - 10.3390/biom12010125 [doi]
LID - 125
AB  - Copper is essential for the stability and activity of cytochrome c oxidase (CcO), 
      the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to 
      COX1 and COX2, two core subunits of CcO, forming the Cu(B) and Cu(A) sites, 
      respectively. Biogenesis of these two copper sites of CcO occurs separately and 
      requires a number of evolutionarily conserved proteins that form the 
      mitochondrial copper delivery pathway. Pathogenic mutations in some of the 
      proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been 
      shown to cause fatal infantile human disorders, highlighting the biomedical 
      significance of understanding copper delivery mechanisms to CcO. While two 
      decades of studies have provided a clearer picture regarding the biochemical 
      roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function 
      of COA6, the new member of this pathway. Initial genetic and biochemical studies 
      have linked COA6 with copper delivery to COX2 and follow-up structural and 
      functional studies have shown that it is specifically required for the biogenesis 
      of the Cu(A) site by acting as a disulfide reductase of SCO and COX2 proteins. 
      Its role as a copper metallochaperone has also been proposed. Here, we critically 
      review the recent literature regarding the molecular function of COA6 in Cu(A) 
      biogenesis.
FAU - Swaminathan, Abhinav B
AU  - Swaminathan AB
AUID- ORCID: 0000-0002-3585-2866
AD  - Department of Biochemistry and Biophysics, Texas A&M University, College Station, 
      TX 77843, USA.
FAU - Gohil, Vishal M
AU  - Gohil VM
AUID- ORCID: 0000-0002-9920-2563
AD  - Department of Biochemistry and Biophysics, Texas A&M University, College Station, 
      TX 77843, USA.
LA  - eng
GR  - R01 GM111672/GM/NIGMS NIH HHS/United States
GR  - R01GM111672/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20220113
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (COA6 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (SCO1 protein, human)
RN  - 789U1901C5 (Copper)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Carrier Proteins/metabolism
MH  - *Copper/metabolism
MH  - *Electron Transport Complex IV/genetics/metabolism
MH  - Humans
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Molecular Chaperones/metabolism
PMC - PMC8773535
OTO - NOTNLM
OT  - COA6
OT  - COX2
OT  - CuA site
OT  - copper
OT  - cytochrome c oxidase
OT  - disulfide reductase
OT  - metallochaperone
OT  - mitochondria
COIS- The authors declare no conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/01/13
CRDT- 2022/01/21 01:05
PHST- 2021/12/16 00:00 [received]
PHST- 2022/01/09 00:00 [revised]
PHST- 2022/01/10 00:00 [accepted]
PHST- 2022/01/21 01:05 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2022/01/13 00:00 [pmc-release]
AID - biom12010125 [pii]
AID - biomolecules-12-00125 [pii]
AID - 10.3390/biom12010125 [doi]
PST - epublish
SO  - Biomolecules. 2022 Jan 13;12(1):125. doi: 10.3390/biom12010125.