Two specific proteins act as personal bodyguards for iron to stop it from turning into a lethal toxin inside the liver.
April 25, 2026
Original Paper
Iron chaperones and RNA-binding proteins, PCBP1 and PCBP2, maintain hepatic iron balance and protect against ferroptosis
SSRN · 6642109
The Takeaway
Iron is a necessary nutrient that becomes extremely dangerous to human cells when it is left floating around freely. The proteins PCBP1 and PCBP2 function as chaperones that escort iron safely through the liver to keep it from causing damage. When these proteins are absent, the liver experiences a massive wave of cell death called ferroptosis. This study shows that the body own iron can effectively eat the liver from the inside out without these specific molecular escorts. This discovery highlights a potential target for treating liver diseases and iron overload disorders. It reveals that iron balance is a fragile system held together by a few critical bodyguards.
From the abstract
Poly rC binding proteins (PCBPs) 1 and 2 bind iron and ssDNA/RNA, acting as iron chaperones for enzyme metalation, ferritin storage, and iron toxicity prevention. Previously, we demonstrated that liver-specific PCBP1 deletion in mice increased unchaperoned iron, causing hepatic oxidative damage and steatosis. Little is known about the functions of PCBP2 in vivo. To define the roles of PCBP1 and PCBP2 in murine hepatic iron metabolism, we generated conditional (Alb-Cre) and vector-mediated (AAV8