TIP47 protects mitochondrial membrane integrity and inhibits oxidative-stress-induced cell death.
We found that overexpression of tail interacting protein of 47 kDa (TIP47), but not its truncated form (t-TIP47) protected NIH3T3 cells from hydrogen-peroxide-induced cell death, prevented the hydrogen-peroxide-induced mitochondrial depolarization determined by 5,50,6,60-tetrachloro-1,10,3,30-tetraethyl-benzimidazolylcarbocyanine iodide (JC1), while suppression of TIP47 in HeLa cells facilitated oxidative-stress-induced cell death. TIP47 was located to the cytoplasm of untreated cells, but some was associated to mitochondria in oxidative stress. Recombinant TIP47, but not t-TIP47 increased the mitochondrial membrane potential (Deltapsi), and partially prevented Ca2+ induced depolarization. It is assumed that TIP47 can bind to mitochondria in oxidative stress, and inhibit mitochondria mediated cell death by protecting mitochondrial membrane integrity.
Hocsak
E
E
Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
Racz
B
B
Szabo
A
A
Mester
L
L
Rapolti
E
E
Pozsgai
E
E
Javor
Sz
S
Bellyei
Sz
S
Gallyas
F
F
Sumegi
B
B
Szigeti
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; C523440:Plin3 protein, mouse; D011257:Pregnancy Proteins; D033921:Vesicular Transport Proteins; D006861:Hydrogen Peroxide