PMID- 15647387
OWN - NLM
STAT- MEDLINE
DCOM- 20050607
LR  - 20220309
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 288
IP  - 6
DP  - 2005 Jun
TI  - Inhibition of complex I of the electron transport chain causes O2-. -mediated 
      mitochondrial outgrowth.
PG  - C1440-50
AB  - Recent evidence indicates that oxidative stress is central to the pathogenesis of 
      a wide variety of degenerative diseases, aging, and cancer. Oxidative stress 
      occurs when the delicate balance between production and detoxification of 
      reactive oxygen species is disturbed. Mammalian cells respond to this condition 
      in several ways, among which is a change in mitochondrial morphology. In the 
      present study, we have used rotenone, an inhibitor of complex I of the 
      respiratory chain, which is thought to increase mitochondrial O(2)(-)* 
      production, and mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to 
      investigate the relationship between mitochondrial O(2)(-)* production and 
      morphology in human skin fibroblasts. Video-rate confocal microscopy of cells 
      pulse loaded with the mitochondria-specific cation rhodamine 123, followed by 
      automated analysis of mitochondrial morphology, revealed that chronic rotenone 
      treatment (100 nM, 72 h) significantly increased mitochondrial length and 
      branching without changing the number of mitochondria per cell. In addition, this 
      treatment caused a twofold increase in lipid peroxidation as determined with 
      C11-BODIPY(581/591). Finally, digital imaging microscopy of cells loaded with 
      hydroethidine, which is oxidized by O(2)(-)* to yield fluorescent ethidium, 
      revealed that chronic rotenone treatment caused a twofold increase in the rate of 
      O(2)(-)* production. MitoQ (10 nM, 72 h) did not interfere with rotenone-induced 
      ethidium formation but abolished rotenone-induced outgrowth and lipid 
      peroxidation. These findings show that increased mitochondrial O(2)(-)* 
      production as a consequence of, for instance, complex I inhibition leads to 
      mitochondrial outgrowth and that MitoQ acts downstream of this O(2)(-)* to 
      prevent alterations in mitochondrial morphology.
FAU - Koopman, Werner J H
AU  - Koopman WJ
AD  - Microscopal Imaging Center, Department of Biochemistry, Nijmegen Center for 
      Molecular Life Sciences, Radboud University Medical Center, PO Box 9101, NL-6500 
      HB Nijmegen, The Netherlands.
FAU - Verkaart, Sjoerd
AU  - Verkaart S
FAU - Visch, Henk-Jan
AU  - Visch HJ
FAU - van der Westhuizen, Francois H
AU  - van der Westhuizen FH
FAU - Murphy, Michael P
AU  - Murphy MP
FAU - van den Heuvel, Lambertus W P J
AU  - van den Heuvel LW
FAU - Smeitink, Jan A M
AU  - Smeitink JA
FAU - Willems, Peter H G M
AU  - Willems PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050112
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Uncoupling Agents)
RN  - 03L9OT429T (Rotenone)
RN  - 11062-77-4 (Superoxides)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
SB  - IM
MH  - Cells, Cultured
MH  - Electron Transport/*physiology
MH  - Electron Transport Complex I/antagonists & inhibitors/*physiology
MH  - Fibroblasts/physiology/ultrastructure
MH  - Humans
MH  - Mitochondria/drug effects/*physiology/ultrastructure
MH  - Rotenone/pharmacology
MH  - Skin/ultrastructure
MH  - Superoxides/*metabolism
MH  - Uncoupling Agents/pharmacology
EDAT- 2005/01/14 09:00
MHDA- 2005/06/09 09:00
CRDT- 2005/01/14 09:00
PHST- 2005/01/14 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2005/01/14 09:00 [entrez]
AID - 00607.2004 [pii]
AID - 10.1152/ajpcell.00607.2004 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2005 Jun;288(6):C1440-50. doi: 
      10.1152/ajpcell.00607.2004. Epub 2005 Jan 12.