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Title: p32, a novel binding partner of Mcl-1, positively regulates mitochondrial Ca{sup 2+} uptake and apoptosis

Highlights: • p32 binds to Mcl-1. • p32 affects apoptosis. • p32 and Mcl-1 regulate mitochondrial Ca{sup 2+}. - Abstract: Mcl-1 is a major anti-apoptotic Bcl-2 family protein. It is well known that Mcl-1 can interact with certain pro-apoptotic Bcl-2 family proteins in normal cells to neutralize their pro-apoptotic functions, thus prevent apoptosis. In addition, it was recently found that Mcl-1 can also inhibit mitochondrial calcium uptake. The detailed mechanism, however, is still not clear. Based on Yeast Two-Hybrid screening and co-immunoprecipitation, we identified a mitochondrial protein p32 (C1qbp) as a novel binding partner of Mcl-1. We found that p32 had a number of interesting properties: (1) p32 can positively regulate UV-induced apoptosis in HeLa cells. (2) Over-expressing p32 could significantly promote mitochondrial calcium uptake, while silencing p32 by siRNA suppressed it. (3) In p32 knockdown cells, Ruthenium Red treatment (an inhibitor of mitochondrial calcium uniporter) showed no further suppressive effect on mitochondrial calcium uptake. In addition, in Ruthenium Red treated cells, Mcl-1 also failed to suppress mitochondrial calcium uptake. Taken together, our findings suggest that p32 is part of the putative mitochondrial uniporter that facilitates mitochondrial calcium uptake. By binding to p32, Mcl-1 can interfere with the uniporter function,more » thus inhibit the mitochondrial Ca{sup 2+} uploading. This may provide a novel mechanism to explain the anti-apoptotic function of Mcl-1.« less
Authors:
 [1] ; ;  [2] ;  [3] ;  [1]
  1. Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China)
  2. School of Medicine, Tsinghua University, Beijing (China)
  3. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai (China)
Publication Date:
OSTI Identifier:
22416721
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 451; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BORON CHLORIDES; CALCIUM; CALCIUM IONS; DMSO; FLUORESCENCE; HELA CELLS; HYBRIDIZATION; MITOCHONDRIA; PROTEINS; RUTHENIUM; SCREENING; UPTAKE; YEASTS