PMID- 29437907
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240323
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 29
IP  - 7
DP  - 2018 Apr 1
TI  - Mitochondrial versus nuclear gene expression and membrane protein assembly: the 
      case of subunit 2 of yeast cytochrome c oxidase.
PG  - 820-833
LID - 10.1091/mbc.E17-09-0560 [doi]
AB  - Deletion of the yeast mitochondrial gene COX2, encoding subunit 2 (mtCox2) of 
      cytochrome c oxidase (CcO), results in a respiratory-incompetent Deltacox2 strain. 
      For a cytosol-synthesized Cox2 to restore respiratory growth, it must carry the 
      W56R mutation (cCox2(W56R)). Nevertheless, only a fraction of cCox2(W56R) is 
      matured in mitochondria, allowing  approximately 60% steady-state accumulation of CcO. This can 
      be attributed either to the point mutation or to an inefficient biogenesis of 
      cCox2(W56R). We generated a strain expressing the mutant protein mtCox2(W56R) 
      inside mitochondria which should follow the canonical biogenesis of 
      mitochondria-encoded Cox2. This strain exhibited growth rates, CcO steady-state 
      levels, and CcO activity similar to those of the wild type; therefore, the 
      efficiency of Cox2 biogenesis is the limiting step for successful allotopic 
      expression. Upon coexpression of cCox2(W56R) and mtCox2, each protein assembled 
      into CcO independently from its genetic origin, resulting in a mixed population 
      of CcO with most complexes containing the mtCox2 version. Notably, the presence 
      of the mtCox2 enhances cCox2(W56R) incorporation. We provide proof of principle 
      that an allotopically expressed Cox2 may complement a phenotype due to a mutant 
      mitochondrial COX2 gene. These results are relevant to developing a rational 
      design of genes for allotopic expression intended to treat human mitochondrial 
      diseases.
FAU - Rubalcava-Gracia, Diana
AU  - Rubalcava-Gracia D
AD  - Departamento de Genetica Molecular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico, 04510 Ciudad Mexico, D. F., Mexico.
FAU - Vazquez-Acevedo, Miriam
AU  - Vazquez-Acevedo M
AD  - Departamento de Genetica Molecular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico, 04510 Ciudad Mexico, D. F., Mexico.
FAU - Funes, Soledad
AU  - Funes S
AD  - Departamento de Genetica Molecular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico, 04510 Ciudad Mexico, D. F., Mexico.
FAU - Perez-Martinez, Xochitl
AU  - Perez-Martinez X
AD  - Departamento de Genetica Molecular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico, 04510 Ciudad Mexico, D. F., Mexico.
FAU - Gonzalez-Halphen, Diego
AU  - Gonzalez-Halphen D
AD  - Departamento de Genetica Molecular, Instituto de Fisiologia Celular, Universidad 
      Nacional Autonoma de Mexico, 04510 Ciudad Mexico, D. F., Mexico.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
SB  - IM
PMC - PMC5905295
EDAT- 2018/02/14 06:00
MHDA- 2018/02/14 06:01
PMCR- 2018/06/16
CRDT- 2018/02/14 06:00
PHST- 2018/02/14 06:00 [pubmed]
PHST- 2018/02/14 06:01 [medline]
PHST- 2018/02/14 06:00 [entrez]
PHST- 2018/06/16 00:00 [pmc-release]
AID - mbc.E17-09-0560 [pii]
AID - E17-09-0560 [pii]
AID - 10.1091/mbc.E17-09-0560 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2018 Apr 1;29(7):820-833. doi: 10.1091/mbc.E17-09-0560.