BNIP3 in melanoma: isn't it IRONic?

Mónica Vara-Pérez; Patrizia Agostinis

doi:10.1080/23723556.2021.1947169

BNIP3 in melanoma: isn't it IRONic?

Mol Cell Oncol. 2021 Aug 2;8(4):1947169. doi: 10.1080/23723556.2021.1947169. eCollection 2021.

Authors

Mónica Vara-Pérez^{1

2}, Patrizia Agostinis^{1

2}

Affiliations

¹ Cell Death Research and Therapy Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
² VIB Center for Cancer Biology,KULeuven, Leuven, Belgium.

Abstract

Melanoma cells exploit mitophagy and hypoxia signaling to promote their growth. In a recent study, we found that loss of B-cell lymphoma 2 (BCL-2)/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3) curbed Hypoxia Inducible Factor 1 alpha (HIF-1α) levels and melanoma growth in vivo. Insufficient levels of BNIP3 boost iron-driven prolyl hydroxylase 2 (Phd2)-mediated degradation of HIF-1α by exacerbating nuclear receptor activator 4 (Ncoa4)-mediated ferritinophagy. Thus, BNIP3 promotes melanoma growth by controlling iron metabolism.

Keywords: BNIP3; HIF-1α; autophagy; ferritinophagy; iron; melanoma; metabolism.

Grants and funding

M.V.P. is the recipient of an FWO Doctoral Fellowship from the Flemish Research Foundation [FWO-Vlaanderen, 1186019N], Belgium. P.A. is supported by grants from the Flemish Research Foundation [FWO-Vlaanderen; G076617N, G049817N, G070115N], the EOS consortium [30837538], Stichting tegen Kanker [FAF-F/2018/1252] and KU Leuven [C16/15/073].