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@ARTICLE{Boix:279376,
      author       = {Boix, Julia and Knuever, Jana and Niehoff, Nadine and Sen,
                      Ayesha and Pla-Martin, David and Baris, Olivier R and Etich,
                      Julia and Brachvogel, Bent and Kaul, Harshita and Isbrandt,
                      Dirk and Soroka, Ekaterina and Bazzi, Hisham and Wenger,
                      Roland H and Giavalisco, Patrick and Wiesner, Rudolf J},
      title        = {{C}onstitutive {HIF}-1α {E}xpression in the {E}pidermis
                      {F}uels {P}roliferation and {I}s {E}ssential for {E}ffective
                      {B}arrier {F}ormation.},
      journal      = {The journal of investigative dermatology},
      volume       = {145},
      number       = {7},
      issn         = {0022-202X},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00753},
      pages        = {1683 - 1692.e8},
      year         = {2025},
      abstract     = {Epidermis is one of the most rapidly proliferating tissues
                      in the body with high demands for adenosine triphosphate and
                      cellular building blocks. In this study, we show that to
                      meet these requirements, keratinocytes constitutively
                      express HIF-1α, even in the presence of oxygen levels
                      sufficient for HIF-1α hydroxylation. We previously reported
                      that mice with severe epidermal mitochondrial dysfunction
                      actually showed a hyperproliferative epidermis but rapidly
                      died of systemic lactic acidosis and hypoglycemia,
                      indicating excessive glycolysis. In this work, we
                      interrogated HIF-1α function in glycolysis by its epidermal
                      ablation combined with mitochondrial dysfunction, which
                      resulted in decreased proliferation but even earlier
                      lethality due to a severe barrier defect. Our data
                      demonstrate that HIF-1α is indispensable for maintaining a
                      high aerobic glycolytic flux necessary for supplying energy
                      but also for synthetizing cellular building blocks such as
                      lipids, which are both essential for proliferation as well
                      as barrier formation. HIF-1α is stabilized in keratinocytes
                      in the presence of oxygen by high levels of HIF-1α
                      transcripts, low levels of prolyl-4-hydroxylases (PHD2 and
                      PHD3), and a low cellular a-ketoglutarate/lactate ratio,
                      likely inhibiting prolyl-4-hydroxylase activity. Our data
                      suggest a key role for constitutive HIF-1α expression
                      allowing a Warburg-like metabolism in healthy, highly
                      proliferative keratinocytes, similar to that in tumor
                      cells.},
      keywords     = {Hypoxia-Inducible Factor 1, alpha Subunit: metabolism /
                      Hypoxia-Inducible Factor 1, alpha Subunit: genetics /
                      Animals / Cell Proliferation / Mice / Epidermis: metabolism
                      / Epidermis: pathology / Keratinocytes: metabolism /
                      Keratinocytes: cytology / Glycolysis / Mitochondria:
                      metabolism / Epidermal barrier function (Other) / HIF-1α
                      (Other) / Lipid synthesis (Other) / Mitochondrial DNA
                      (Other) / Skin homeostasis (Other) / Hypoxia-Inducible
                      Factor 1, alpha Subunit (NLM Chemicals) / Hif1a protein,
                      mouse (NLM Chemicals)},
      cin          = {AG Isbrandt},
      ddc          = {610},
      cid          = {I:(DE-2719)1011003},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39580109},
      doi          = {10.1016/j.jid.2024.09.022},
      url          = {https://pub.dzne.de/record/279376},
}