PMID- 26030260
OWN - NLM
STAT- MEDLINE
DCOM- 20150907
LR  - 20181113
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 54
IP  - 24
DP  - 2015 Jun 23
TI  - Hypoxia Inducible Factors Modulate Mitochondrial Oxygen Consumption and 
      Transcriptional Regulation of Nuclear-Encoded Electron Transport Chain Genes.
PG  - 3739-48
LID - 10.1021/bi5012892 [doi]
AB  - Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription 
      factor that is activated with a decrease in oxygen availability. HIF1 regulates 
      the expression of genes involved in a cell's adaptation to hypoxic stress, 
      including those with mitochondrial specific function. To gain a more 
      comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we 
      studied the link between hypoxia, HIF1 transactivation, and electron transport 
      chain (ETC) function. We established immortalized mouse embryonic fibroblasts 
      (MEFs) for HIF1alpha wild-type (WT) and null cells and tested whether HIF1alpha regulates 
      mitochondrial respiration by modulating gene expressions of nuclear-encoded ETC 
      components. High-throughput quantitative real-time polymerase chain reaction was 
      performed to screen nuclear-encoded mitochondrial genes related to the ETC to 
      identify those whose regulation was HIF1alpha-dependent. Our data suggest that HIF1alpha 
      regulates transcription of cytochrome c oxidase (CcO) heart/muscle isoform 7a1 
      (Cox7a1) under hypoxia, where it is induced 1.5-2.5-fold, whereas Cox4i2 hypoxic 
      induction was HIF1alpha-independent. We propose that adaptation to hypoxic stress of 
      CcO as the main cellular oxygen consumer is mediated by induction of 
      hypoxia-sensitive tissue-specific isoforms. We suggest that HIF1 plays a central 
      role in maintaining homeostasis in cellular respiration during hypoxic stress via 
      regulation of CcO activity.
FAU - Hwang, Hye Jin
AU  - Hwang HJ
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - Lynn, Scott G
AU  - Lynn SG
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - Vengellur, Ajith
AU  - Vengellur A
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - Saini, Yogesh
AU  - Saini Y
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - Grier, Elizabeth A
AU  - Grier EA
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - Ferguson-Miller, Shelagh M
AU  - Ferguson-Miller SM
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
FAU - LaPres, John J
AU  - LaPres JJ
AD  - daggerDepartment of Biochemistry and Molecular Biology, double daggerCenter for Integrative 
      Toxicology, and  section signCenter for Mitochondrial Science and Medicine, Michigan State 
      University, East Lansing, Michigan 48824-1319, United States.
LA  - eng
GR  - R01 GM026916/GM/NIGMS NIH HHS/United States
GR  - T32 ES007255/ES/NIEHS NIH HHS/United States
GR  - T32ES007255-19/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150612
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 1.9.3.1 (cytochrome c oxidase subunit 7a1, mouse)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Clone Cells
MH  - Electron Transport Complex IV/antagonists & inhibitors/genetics/*metabolism
MH  - Embryo, Mammalian/cytology/metabolism
MH  - *Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Profiling
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondria/drug effects/enzymology/*metabolism
MH  - Oxidative Phosphorylation/drug effects
MH  - *Oxygen Consumption/drug effects
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Transcriptional Activation/drug effects
PMC - PMC5957085
MID - NIHMS965231
COIS- Notes The authors declare no competing financial interest.
EDAT- 2015/06/02 06:00
MHDA- 2015/09/08 06:00
PMCR- 2018/05/17
CRDT- 2015/06/02 06:00
PHST- 2015/06/02 06:00 [entrez]
PHST- 2015/06/02 06:00 [pubmed]
PHST- 2015/09/08 06:00 [medline]
PHST- 2018/05/17 00:00 [pmc-release]
AID - 10.1021/bi5012892 [doi]
PST - ppublish
SO  - Biochemistry. 2015 Jun 23;54(24):3739-48. doi: 10.1021/bi5012892. Epub 2015 Jun 
      12.