The University of Bradford Institutional Repository

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 melanocytes 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 MC and induced slight hypopigmentation of epidermis in mice. The melanin content of hair was decreased by 10-15% in mice with autophagy-deficient MC as compared to control animals. When cultured in vitro , MC from mutant and control mice produced equal amounts of melanin per cell. However, Atg7 -deficient MC entered into premature growth arrest and accumulated reactive oxygen species (ROS) damage, ubiquitinated proteins and the multi-functional adaptor protein SQSTM1/p62. Moreover, nuclear factor erythroid 2–related factor 2 (Nrf2)- dependent expression of NAD(P)H dehydrogenase, quinone 1 (Nqo1) and glutathione S-transferase Mu 1 (Gstm1) was increased, indicating a contribution of autophagy to redox homeostasis in MC. 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 MC.