title: Holocrine Secretion of Sebum Is a Unique DNase2-Dependent Mode of Programmed Cell Death.
abstract: Sebaceous glands produce sebum via holocrine secretion, a largely uncharacterized mode of programmed cell death that contributes to the homeostasis and barrier function of the skin. To determine the mechanism of DNA degradation during sebocyte cell death, we have inactivated candidate DNA-degrading enzymes by targeted gene deletions in mice. DNase1 and DNase1-like 2 were dispensable for nuclear DNA degradation in sebocytes. By contrast, epithelial cell-specific deletion of lysosomal DNase2 blocked DNA degradation in these cells. DNA breakdown during sebocyte differentiation coincided with the loss of LAMP1 and was accelerated by the abrogation of autophagy, the central cellular program of lysosome-dependent catabolism. Suppression of DNA degradation by the deletion of DNase2 resulted in aberrantly increased concentrations of residual DNA and decreased amounts of the DNA metabolite uric acid in secreted sebum. These results define holocrine secretion as a DNase2-mediated form of programmed cell death and suggest that autophagy-dependent metabolism, DNA degradation, and the molecular composition of sebum are mechanistically linked.
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Heinz
authors: H
authors: Fischer
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Judith
authors: J
authors: Fumicz
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Heidemarie
authors: H
authors: Rossiter
authors: Department of Anatomy and Molecular Embryology, Medical Faculty, Ruhr-University Bochum, Bochum, Germany.
authors: Markus
authors: M
authors: Napirei
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Maria
authors: M
authors: Buchberger
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Erwin
authors: E
authors: Tschachler
authors: Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: leopold.eckhart@meduniwien.ac.at.
authors: Leopold
authors: L
authors: Eckhart
mesh_terms: D000818:Animals; D017209:Apoptosis; D004247:DNA; D004272:DNA, Mitochondrial / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D006657:Histones / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012627:Sebaceous Glands / Q000378:metabolism*; D012629:Sebum / Q000166:cytology*; D012867:Skin / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D004247:DNA; D004272:DNA, Mitochondrial; D004706:Endodeoxyribonucleases; D006657:Histones; D051907:Lysosomal Membrane Proteins; D014527:Uric Acid; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C019329:deoxyribonuclease II