The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells

Olivier R. Baris, Anke Klose, Jennifer E. Kloepper, Daniela Weiland, Johannes F.G. Neuhaus, Matthias Schauen, Anna Wille, Alexander Müller, Carsten Merkwirth, Thomas Langer, Nils Göran Larsson, Thomas Krieg, Desmond J. Tobin, Ralf Paus, Rudolf J. Wiesner

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1459-1468
Number of pages10
JournalStem Cells
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Fingerprint

Electron Transport
Stem Cells
Epidermis
Keratin-14
Mitochondrial Dynamics
Skin
Mitochondrial Membranes
Embryonic Stem Cells
Transgenes
Mitochondrial DNA
Dehydration
Germ Cells
Malnutrition
Reactive Oxygen Species
Respiration
Alleles
Parturition
Apoptosis
Phenotype
Cell Line

Keywords

  • Epidermal development
  • Mitochondrial dynamics
  • Oxidative metabolism
  • Stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Baris, O. R., Klose, A., Kloepper, J. E., Weiland, D., Neuhaus, J. F. G., Schauen, M., ... Wiesner, R. J. (2011). The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells. Stem Cells, 29(9), 1459-1468. https://doi.org/10.1002/stem.695

The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells. / Baris, Olivier R.; Klose, Anke; Kloepper, Jennifer E.; Weiland, Daniela; Neuhaus, Johannes F.G.; Schauen, Matthias; Wille, Anna; Müller, Alexander; Merkwirth, Carsten; Langer, Thomas; Larsson, Nils Göran; Krieg, Thomas; Tobin, Desmond J.; Paus, Ralf; Wiesner, Rudolf J.

In: Stem Cells, Vol. 29, No. 9, 01.09.2011, p. 1459-1468.

Research output: Contribution to journalArticle

Baris, OR, Klose, A, Kloepper, JE, Weiland, D, Neuhaus, JFG, Schauen, M, Wille, A, Müller, A, Merkwirth, C, Langer, T, Larsson, NG, Krieg, T, Tobin, DJ, Paus, R & Wiesner, RJ 2011, 'The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells', Stem Cells, vol. 29, no. 9, pp. 1459-1468. https://doi.org/10.1002/stem.695
Baris, Olivier R. ; Klose, Anke ; Kloepper, Jennifer E. ; Weiland, Daniela ; Neuhaus, Johannes F.G. ; Schauen, Matthias ; Wille, Anna ; Müller, Alexander ; Merkwirth, Carsten ; Langer, Thomas ; Larsson, Nils Göran ; Krieg, Thomas ; Tobin, Desmond J. ; Paus, Ralf ; Wiesner, Rudolf J. / The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells. In: Stem Cells. 2011 ; Vol. 29, No. 9. pp. 1459-1468.
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