PMID- 18843528
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20220410
IS  - 0145-479X (Print)
IS  - 0145-479X (Linking)
VI  - 40
IP  - 5
DP  - 2008 Oct
TI  - Regulation of oxidative phosphorylation, the mitochondrial membrane potential, 
      and their role in human disease.
PG  - 445-56
LID - 10.1007/s10863-008-9169-3 [doi]
AB  - Thirty years after Peter Mitchell was awarded the Nobel Prize for the 
      chemiosmotic hypothesis, which links the mitochondrial membrane potential 
      generated by the proton pumps of the electron transport chain to ATP production 
      by ATP synthase, the molecular players involved once again attract attention. 
      This is so because medical research increasingly recognizes mitochondrial 
      dysfunction as a major factor in the pathology of numerous human diseases, 
      including diabetes, cancer, neurodegenerative diseases, and ischemia reperfusion 
      injury. We propose a model linking mitochondrial oxidative phosphorylation 
      (OxPhos) to human disease, through a lack of energy, excessive free radical 
      production, or a combination of both. We discuss the regulation of OxPhos by cell 
      signaling pathways as a main regulatory mechanism in higher organisms, which in 
      turn determines the magnitude of the mitochondrial membrane potential: if too 
      low, ATP production cannot meet demand, and if too high, free radicals are 
      produced. This model is presented in light of the recently emerging understanding 
      of mechanisms that regulate mammalian cytochrome c oxidase and its substrate 
      cytochrome c as representative enzymes for the entire OxPhos system.
FAU - Huttemann, Maik
AU  - Huttemann M
AD  - Center for Molecular Medicine and Genetics, Wayne State University School of 
      Medicine, Detroit, MI 48201, USA. mhuttema@med.wayne.edu
FAU - Lee, Icksoo
AU  - Lee I
FAU - Pecinova, Alena
AU  - Pecinova A
FAU - Pecina, Petr
AU  - Pecina P
FAU - Przyklenk, Karin
AU  - Przyklenk K
FAU - Doan, Jeffrey W
AU  - Doan JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20081009
PL  - United States
TA  - J Bioenerg Biomembr
JT  - Journal of bioenergetics and biomembranes
JID - 7701859
RN  - 0 (Free Radicals)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Allosteric Regulation
MH  - Cytochromes c/chemistry/metabolism
MH  - Electron Transport Complex IV/antagonists & inhibitors/chemistry/metabolism
MH  - Free Radicals/metabolism
MH  - Humans
MH  - *Membrane Potential, Mitochondrial
MH  - Mitochondrial Diseases/*etiology/*metabolism
MH  - *Models, Biological
MH  - Models, Molecular
MH  - Nitric Oxide/metabolism
MH  - *Oxidative Phosphorylation
MH  - Proton-Motive Force
MH  - Signal Transduction
RF  - 106
EDAT- 2008/10/10 09:00
MHDA- 2009/02/21 09:00
CRDT- 2008/10/10 09:00
PHST- 2008/06/04 00:00 [received]
PHST- 2008/07/01 00:00 [accepted]
PHST- 2008/10/10 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/10/10 09:00 [entrez]
AID - 10.1007/s10863-008-9169-3 [doi]
PST - ppublish
SO  - J Bioenerg Biomembr. 2008 Oct;40(5):445-56. doi: 10.1007/s10863-008-9169-3. Epub 
      2008 Oct 9.