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Autophagy. 2020 Jan 3:1-7. doi: 10.1080/15548627.2019.1709764. [Epub ahead of print]

ATG7 is essential for secretion of iron from ameloblasts and normal growth of murine incisors during aging.

Author information

1
Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
2
Department of Oral Biology, Medical University of Vienna, Vienna, Austria.
3
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
4
Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.

Abstract

The incisors of rodents comprise an iron-rich enamel and grow throughout adult life, making them unique models of iron metabolism and tissue homeostasis during aging. Here, we deleted Atg7 (autophagy related 7) in murine ameloblasts, i.e. the epithelial cells that produce enamel. The absence of ATG7 blocked the transport of iron from ameloblasts into the maturing enamel, leading to a white instead of yellow surface of maxillary incisors. In aging mice, lack of ATG7 was associated with the growth of ectopic incisors inside severely deformed primordial incisors. These results suggest that 2 characteristic features of rodent incisors, i.e. deposition of iron on the enamel surface and stable growth during aging, depend on autophagic activity in ameloblasts.Abbreviations: ATG5: autophagy related 5; ATG7: autophagy related 7; CMV: cytomegalovirus; Cre: Cre recombinase; CT: computed tomography; FTH1: ferritin heavy polypeptide 1; GFP: green fluorescent protein; KRT5: keratin 5; KRT14: keratin 14; LGALS3: lectin, galactose binding, soluble 3; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NCOA4: nuclear receptor coactivator 4; NRF2: nuclear factor, erythroid 2 like 2; SQSTM1: sequestosome 1.

KEYWORDS:

ATG7; Aging; ameloblast; autophagy; epithelium; ferritin; hyperplasia; iron; secretion; tooth

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