PMID- 24494190
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20220321
IS  - 2213-2317 (Print)
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 2
DP  - 2014
TI  - Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial 
      dysfunction in macrophages, kidney fibroblasts and in chronic alcohol 
      hepatotoxicity.
PG  - 273-83
LID - 10.1016/j.redox.2013.07.004 [doi]
AB  - The inducible form of Heme Oxygenase-1 (HO-1), a major endoplasmic reticulum (ER) 
      associated heme protein, is known to play important roles in protection against 
      oxidative and chemical stress by degrading free heme released from degradation of 
      heme proteins. In this study we show that induced expression of HO-1 by 
      subjecting macrophage RAW-264.7 cells to chemical or physiological hypoxia 
      resulted in significant translocation of HO-1 protein to mitochondria. Transient 
      transfection of COS-7 cells with cloned cDNA also resulted in mitochondrial 
      translocation of HO-1. Deletion of N-terminal ER targeting domain increased 
      mitochondrial translocation under the transient transfection conditions. 
      Mitochondrial localization of both intact HO-1 and N-terminal truncated HO-1 
      caused loss of heme aa-3 and cytochrome c oxidase (CcO) activity in COS-7 cells. 
      The truncated protein, which localizes to mitochondria at higher levels, induced 
      substantially steeper loss of CcO activity and reduced heme aa3 content. 
      Furthermore, cells expressing mitochondria targeted HO-1 also induced higher ROS 
      production. Consistent with dysfunctional state of mitochondria induced by HO-1, 
      the mitochondrial recruitment of autophagy markers LC-3 and Drp-1 was also 
      increased in these cells. Chronic ethanol feeding in rats also caused an increase 
      in mitochondrial HO-1 and decrease in CcO activity. These results show that as 
      opposed to the protective effect of the ER associated HO-1, mitochondria targeted 
      HO-1 under normoxic conditions induces mitochondrial dysfunction.
FAU - Bansal, Seema
AU  - Bansal S
AD  - The Department of Animal Biology and the Mari Lowe Center for Comparative 
      Oncology, School of Veterinary Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA.
FAU - Biswas, Gopa
AU  - Biswas G
AD  - The Department of Animal Biology and the Mari Lowe Center for Comparative 
      Oncology, School of Veterinary Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA.
FAU - Avadhani, Narayan G
AU  - Avadhani NG
AD  - The Department of Animal Biology and the Mari Lowe Center for Comparative 
      Oncology, School of Veterinary Medicine, University of Pennsylvania, 
      Philadelphia, PA 19104, USA.
LA  - eng
GR  - R01 AA017749/AA/NIAAA NIH HHS/United States
GR  - R01 GM034883/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20130723
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Membrane Proteins)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Hypoxia
MH  - Chlorocebus aethiops
MH  - Disease Models, Animal
MH  - Electron Transport Complex IV/metabolism
MH  - Fibroblasts/cytology/enzymology
MH  - Heme Oxygenase (Decyclizing)/genetics/*metabolism
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Kidney/cytology/*enzymology
MH  - Liver Diseases, Alcoholic/*enzymology
MH  - Macrophages/cytology/*enzymology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mitochondria/*enzymology
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC3909819
OTO - NOTNLM
OT  - Autophagy
OT  - CcO, cytochrome c oxidase
OT  - Cytochrome c Oxidase
OT  - DCFH-DA, Dichlorofluorescein diacetate
OT  - ER, Endoplasmic reticulum
OT  - HO-1, Heme Oxygenase-1
OT  - Heme aa3 content
OT  - Heme oxygenase-1
OT  - Mitochondrial targeting
OT  - NPR, NADPH cytochrome P 450 reductase
OT  - ROS production
OT  - ROS, Reactive Oxygen Species
EDAT- 2014/02/05 06:00
MHDA- 2014/02/05 06:01
PMCR- 2013/07/23
CRDT- 2014/02/05 06:00
PHST- 2013/07/02 00:00 [received]
PHST- 2013/07/16 00:00 [revised]
PHST- 2013/07/16 00:00 [accepted]
PHST- 2014/02/05 06:00 [entrez]
PHST- 2014/02/05 06:00 [pubmed]
PHST- 2014/02/05 06:01 [medline]
PHST- 2013/07/23 00:00 [pmc-release]
AID - S2213-2317(13)00056-6 [pii]
AID - 10.1016/j.redox.2013.07.004 [doi]
PST - epublish
SO  - Redox Biol. 2013 Jul 23;2:273-83. doi: 10.1016/j.redox.2013.07.004. eCollection 
      2014.