Heat shock protein 70 inhibits the nuclear import of apoptosis-inducing factor to avoid DNA fragmentation in TF-1 cells during erythropoiesis

Loss of mitochondrial membrane potential (ΔΨm) and release of AIF (apoptosis-inducing factor) from mitochondria are key steps in apoptosis. In TF-1 model, ΔΨm was depolarized with AIF release during erythroid development. Yet, no DNA fragmentation was observed. When ΔΨm depolarization had been blocked, erythropoiesis was suppressed. Interestingly, heat shock protein 70 (Hsp70) was found transiently upregulated during depolarization and it retained AIF in the cytosol to avoid DNA damages. When Hsp inhibitor was added, DNA fragmentation occurred. We show this mechanism for the first time in erythropoiesis how cells with ΔΨm depolarization and AIF release escape apoptosis.