Macroautophagy (hereafter referred to as autophagy) involves an intracellular degradation
and recycling system that, in a context-dependent manner, can either promote cell
survival or accelerate cellular demise. Ferroptosis was originally defined in 2012
as an iron-dependent form of cancer cell death different from apoptosis, necrosis,
and autophagy. However, this latter assumption came into question because, in response
to ferroptosis activators (e.g., erastin and RSL3), autophagosomes accumulate, and
because components of the autophagy machinery (e.g., ATG3, ATG5, ATG4B, ATG7, ATG13,
and BECN1) contribute to ferroptotic cell death. In particular, NCOA4-facilitated
ferritinophagy, RAB7A-dependent lipophagy, BECN1-mediated system xc- inhibition, STAT3-induced
lysosomal membrane permeabilization, and HSP90-associated chaperone-mediated autophagy
can promote ferroptosis. In this review, we summarize current knowledge on the signaling
pathways involved in ferroptosis, while focusing on the regulation of autophagy-dependent
ferroptotic cell death. The molecular comprehension of these phenomena may lead to
the development of novel anticancer therapies.