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Suppression of Autophagy Dysregulates the Antioxidant Response and Causes Premature Senescence of Melanocytes
Zhang, C.F. Gruber, F. Mildner, M. Koenig, U. Karner, S. Barresi, C. Rossiter, H. Narzt, M.S. Nagelreiter, I.M. Larue, L.
Zhang, C.F.
Gruber, F.
Mildner, M.
Koenig, U.
Karner, S.
Barresi, C.
Rossiter, H.
Narzt, M.S.
Nagelreiter, I.M.
Larue, L.
Publication Date
2015-05
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openAccess
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2014-09-24
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Abstract
Autophagy is the central cellular mechanism for delivering organelles and cytoplasm to lysosomes for
degradation and recycling of their molecular components. To determine the contribution of autophagy to
melanocyte (MC) biology, we inactivated the essential autophagy gene Atg7 specifically in MCs using the Cre-loxP
system. This gene deletion efficiently suppressed a key step in autophagy, lipidation of microtubule-associated
protein 1 light chain 3 beta (LC3), in MCs and induced slight hypopigmentation of the epidermis in mice. The
melanin content of hair was decreased by 10–15% in mice with autophagy-deficient MC as compared with control
animals. When cultured in vitro, MCs from mutant and control mice produced equal amounts of melanin per cell.
However, Atg7-deficient MCs entered into premature growth arrest and accumulated reactive oxygen species
(ROS) damage, ubiquitinated proteins, and the multi-functional adapter protein SQSTM1/p62. Moreover, nuclear
factor erythroid 2–related factor 2 (Nrf2)–dependent expression of NAD(P)H dehydrogenase, quinone 1, and
glutathione S-transferase Mu 1 was increased, indicating a contribution of autophagy to redox homeostasis in
MCs. In summary, the results of our study suggest that Atg7-dependent autophagy is dispensable for
melanogenesis but necessary for achieving the full proliferative capacity of MCs.
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Zhang C, Gruber F, Ni C et al (2015) Suppression of Autophagy Dysregulates the Antioxidant Response and Causes Premature Senescence of Melanocytes. Journal of Investigative Dermatology. 135(5): 1348-1357.
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