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Abstract

Autophagy is a highly conserved lysosomal degradation pathway in eukaryotic cells that is upregulated in response to stress stimuli. A double membrane vesicle called the autophagosome mediates the degradation of cytoplasmic components. A crucial step of the membrane rearrangements leading to the formation of the autophagosome is the generation of PtdIns(3)P. Subsequently the human WIPI proteins are recruited to fulfill essential functions as PtdIns(3)P effector proteins. NudC, a conserved microtubuli-associated protein was recently identified in a proteome analysis of the human WIPI proteins (Bakula et al., 2017). In this study it was confirmed that NudC interacts with WIPI1, WIPI2 and WIPI4 (Bakula et al., 2017). Subsequent characterizations revealed that NudC is a new autophagy inhibitor. The inhibitory function of NudC is demonstrated by the results that a reduced NudC protein expression (1) increases the number of WIPI1-, WIPI2-, and LC3- positive autophagosomes, (2) reduces the levels of p62 in human tumor cells, (3) increases the rate of long-lived protein degradation and lastly (4) increases the number of autophagosomes observed in electron microscopy analysis. Likewise, overexpression of NudC reduces the number of autophagosomes. We suggest that NudC regulates WIPI-mediated autophagy, perhaps by preventing WIPI proteins from localizing to PtdIns(3)P-enriched membranes.