Immunohistochemistry of ferritin from livers with (left) and without (right) NCOA4 expression. Ferritin accumulates in livers without NCOA4 as NCOA4 is critical for the turnover of ferritin via selective autophagy.
Naiara Santana-Codina and Sebastian Gableske are co-first authors on a paper from the lab identifying a cell autonomous role of NCOA4 in erythropoiesis. Joe initially discovered NCOA4 as the selective autophagy receptor for ferritin, the cellular iron storage complex, during his post-doctoral work. Prior work in the lab identified that loss of NCOA4 perturbs cellular iron homeostasis. While we initially discovered this process in pancreatic cancer cells, we realized that this process is more generalized to all cells. Therefore, we hypothesized that loss of NCOA4 in an organism (a mouse in this instance) would perturb systemic iron homeostasis and the most iron-dependent process in mammals: normal erythropoiesis (red blood cell production). To address these questions, we developed novel conditional knockout mouse models of NCOA4 and performed targeted deletion of NCOA4 in red blood cells as well as induced acute systemic NCOA4 loss in adult mouse. Our work was the first to show a critical role of NCOA4 in adult animals for maintaining iron homeostasis and a role for NCOA4 in maintaining erythropoiesis. Paper is here: Haematologica and on PubMed Central.
Next, we will look at the effects of NCOA4 loss (and gain) in pancreatic tumors given these tumors highly upregulate autophagy and rely on high levels of iron. Stay tuned for further results!
Lab publishes a paper in Haematologica: NCOA4 Maintains Murine Erythropoiesis Via Cell Autonomous And Non-Autonomous Mechanisms