PMID- 31555154
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230705
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Knockdown of APOPT1/COA8 Causes Cytochrome c Oxidase Deficiency, Neuromuscular 
      Impairment, and Reduced Resistance to Oxidative Stress in Drosophila 
      melanogaster.
PG  - 1143
LID - 10.3389/fphys.2019.01143 [doi]
LID - 1143
AB  - Cytochrome c oxidase (COX) deficiency is the biochemical hallmark of several 
      mitochondrial disorders, including subjects affected by mutations in 
      apoptogenic-1 (APOPT1), recently renamed as COA8 (HGNC:20492). Loss-of-function 
      mutations are responsible for a specific infantile or childhood-onset 
      mitochondrial leukoencephalopathy with a chronic clinical course. Patients 
      deficient in COA8 show specific COX deficiency with distinctive neuroimaging 
      features, i.e., cavitating leukodystrophy. In human cells, COA8 is rapidly 
      degraded by the ubiquitin-proteasome system, but oxidative stress stabilizes the 
      protein, which is then involved in COX assembly, possibly by protecting the 
      complex from oxidative damage. However, its precise function remains unknown. The 
      CG14806 gene (dCOA8) is the Drosophila melanogaster ortholog of human COA8 
      encoding a highly conserved COA8 protein. We report that dCOA8 knockdown (KD) 
      flies show locomotor defects, and other signs of neurological impairment, reduced 
      COX enzymatic activity, and reduced lifespan under oxidative stress conditions. 
      Our data indicate that KD of dCOA8 in Drosophila phenocopies several features of 
      the human disease, thus being a suitable model to characterize the molecular 
      function/s of this protein in vivo and the pathogenic mechanisms associated with 
      its defects.
FAU - Brischigliaro, Michele
AU  - Brischigliaro M
AD  - Department of Biology, University of Padova, Padua, Italy.
FAU - Corra, Samantha
AU  - Corra S
AD  - Department of Biology, University of Padova, Padua, Italy.
FAU - Tregnago, Claudia
AU  - Tregnago C
AD  - Department of Women and Children's Health, University of Padova, Padua, Italy.
FAU - Fernandez-Vizarra, Erika
AU  - Fernandez-Vizarra E
AD  - MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United 
      Kingdom.
FAU - Zeviani, Massimo
AU  - Zeviani M
AD  - MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United 
      Kingdom.
AD  - Department of Neurosciences, University of Padova, Padua, Italy.
FAU - Costa, Rodolfo
AU  - Costa R
AD  - Department of Biology, University of Padova, Padua, Italy.
FAU - De Pitta, Cristiano
AU  - De Pitta C
AD  - Department of Biology, University of Padova, Padua, Italy.
LA  - eng
GR  - MC_EX_MR/P007031/1/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00015/8/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_1002/1/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00015/5/MRC_/Medical Research Council/United Kingdom
GR  - MRF_MRF-155-0001-S-MARTI/MRF/MRF/United Kingdom
GR  - MRF_MRF-155-0005-RG-ZEVI-C0784/MRF/MRF/United Kingdom
GR  - MRF_MRF-155-0002-RG-ZEVIA/MRF/MRF/United Kingdom
PT  - Journal Article
DEP - 20190906
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6742693
OTO - NOTNLM
OT  - APOPT1
OT  - Drosophila melanogaster
OT  - cytochrome c oxidase deficiency
OT  - knockdown models
OT  - mitochondrial disease
OT  - resistance to oxidative stress
EDAT- 2019/09/27 06:00
MHDA- 2019/09/27 06:01
PMCR- 2019/09/06
CRDT- 2019/09/27 06:00
PHST- 2019/05/18 00:00 [received]
PHST- 2019/08/22 00:00 [accepted]
PHST- 2019/09/27 06:00 [entrez]
PHST- 2019/09/27 06:00 [pubmed]
PHST- 2019/09/27 06:01 [medline]
PHST- 2019/09/06 00:00 [pmc-release]
AID - 10.3389/fphys.2019.01143 [doi]
PST - epublish
SO  - Front Physiol. 2019 Sep 6;10:1143. doi: 10.3389/fphys.2019.01143. eCollection 
      2019.