PMID- 21780252
OWN - NLM
STAT- MEDLINE
DCOM- 20120216
LR  - 20220223
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 29
IP  - 9
DP  - 2011 Sep
TI  - The mitochondrial electron transport chain is dispensable for proliferation and 
      differentiation of epidermal progenitor cells.
PG  - 1459-68
LID - 10.1002/stem.695 [doi]
AB  - Tissue stem cells and germ line or embryonic stem cells were shown to have 
      reduced oxidative metabolism, which was proposed to be an adaptive mechanism to 
      reduce damage accumulation caused by reactive oxygen species. However, an 
      alternate explanation is that stem cells are less dependent on specialized 
      cytoplasmic functions compared with differentiated cells, therefore, having a 
      high nuclear-to-cytoplasmic volume ratio and consequently a low mitochondrial 
      content. To determine whether stem cells rely or not on mitochondrial 
      respiration, we selectively ablated the electron transport chain in the basal 
      layer of the epidermis, which includes the epidermal progenitor/stem cells 
      (EPSCs). This was achieved using a loxP-flanked mitochondrial transcription 
      factor A (Tfam) allele in conjunction with a keratin 14 Cre transgene. The 
      epidermis of these animals (Tfam(EKO)) showed a profound depletion of 
      mitochondrial DNA and complete absence of respiratory chain complexes. However, 
      despite a short lifespan due to malnutrition, epidermal development and skin 
      barrier function were not impaired. Differentiation of epidermal layers was 
      normal and no proliferation defect or major increase of apoptosis could be 
      observed. In contrast, mice with an epidermal ablation of prohibitin-2, a 
      scaffold protein in the inner mitochondrial membrane, displayed a dramatic 
      phenotype observable already in utero, with severely impaired skin architecture 
      and barrier function, ultimately causing death from dehydration shortly after 
      birth. In conclusion, we here provide unequivocal evidence that EPSCs, and 
      probably tissue stem cells in general, are independent of the mitochondrial 
      respiratory chain, but still require a functional dynamic mitochondrial 
      compartment.
CI  - Copyright (c) 2011 AlphaMed Press.
FAU - Baris, Olivier R
AU  - Baris OR
AD  - Center for Physiology and Pathophysiology, Institute for Vegetative 
      Physiology,University of Cologne, Cologne, Germany.
FAU - Klose, Anke
AU  - Klose A
FAU - Kloepper, Jennifer E
AU  - Kloepper JE
FAU - Weiland, Daniela
AU  - Weiland D
FAU - Neuhaus, Johannes F G
AU  - Neuhaus JF
FAU - Schauen, Matthias
AU  - Schauen M
FAU - Wille, Anna
AU  - Wille A
FAU - Muller, Alexander
AU  - Muller A
FAU - Merkwirth, Carsten
AU  - Merkwirth C
FAU - Langer, Thomas
AU  - Langer T
FAU - Larsson, Nils-Goran
AU  - Larsson NG
FAU - Krieg, Thomas
AU  - Krieg T
FAU - Tobin, Desmond J
AU  - Tobin DJ
FAU - Paus, Ralf
AU  - Paus R
FAU - Wiesner, Rudolf J
AU  - Wiesner RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (High Mobility Group Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tfam protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Differentiation/physiology
MH  - Cell Growth Processes/physiology
MH  - DNA-Binding Proteins/deficiency/genetics/metabolism
MH  - Electron Transport
MH  - *Epidermal Cells
MH  - Epidermis/metabolism
MH  - Genotype
MH  - High Mobility Group Proteins/deficiency/genetics/metabolism
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/genetics/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Stem Cells/*cytology/*metabolism
EDAT- 2011/07/23 06:00
MHDA- 2012/02/18 06:00
CRDT- 2011/07/23 06:00
PHST- 2011/07/23 06:00 [entrez]
PHST- 2011/07/23 06:00 [pubmed]
PHST- 2012/02/18 06:00 [medline]
AID - 10.1002/stem.695 [doi]
PST - ppublish
SO  - Stem Cells. 2011 Sep;29(9):1459-68. doi: 10.1002/stem.695.