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 (DeltaPsi(m)) and release of AIF (apoptosis-inducing factor) from mitochondria are key steps in apoptosis. In TF-1 model, DeltaPsi(m) was depolarized with AIF release during erythroid development. Yet, no DNA fragmentation was observed. When DeltaPsi(m) 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 DeltaPsi(m) depolarization and AIF release escape apoptosis.
Lui
Julian Chun-Kin
JC
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Kong
Siu-Kai
SK
D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002460:Cell Line; D053938:DNA Fragmentation; D004920:Erythropoiesis / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D051033:Apoptosis Inducing Factor; D018840:HSP70 Heat-Shock Proteins