The fast-mobility isoform of mouse Mcl-1 is a mitochondrial matrix-localized protein with attenuated anti-apoptotic activity

FEBS Letters
Chi-Ruei Huang, Hsin-Fang Yang-Yen

Abstract

The full-length pro-survival protein Mcl-1 predominantly resides on the outer membrane of mitochondria. Here, we identified a mitochondrial matrix-localized isoform of Mcl-1 that lacks 33 amino acid residues at the N-terminus which serve both as a mitochondrial targeting and processing signal. Ectopically-expressed Mcl-1 without the N-terminal 33 residues failed to enter the mitochondrial matrix but retained wt-like activities both for interaction with BH3-only proteins and anti-apoptosis. In contrast, the mitochondrial matrix-localized isoform failed to interact with BH3-only proteins and manifested an attenuated anti-apoptotic activity. This study reveals that import of Mcl-1 into the mitochondrial matrix results in the attenuation of Mcl-1's anti-apoptotic function.

References

Nov 2, 1984·European Journal of Biochemistry·B SchmidtW Neupert
Nov 1, 1996·European Journal of Biochemistry·M G Claros, P Vincens
Nov 25, 2003·Genes & Development·Andrea CuconatiEileen White
Dec 12, 2003·Nature·Joseph T OpfermanStanley J Korsmeyer
Feb 26, 2004·Nature Structural & Molecular Biology·Christian KozanyKai Hell
Feb 19, 2005·Science·Joseph T OpfermanStanley J Korsmeyer
Mar 31, 2005·Molecular and Cellular Biology·Hsuan LiuHsin-Fang Yang-Yen
Jul 11, 2006·Molecular Biology of the Cell·Chiang-Hung ChouHsin-Fang Yang-Yen
Jan 8, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Binje VickHenning Schulze-Bergkamen
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chia-Yu YangHsin-Fang Yang-Yen
Aug 8, 2009·Annual Review of Genetics·Chunxin Wang, Richard J Youle
Aug 14, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hayato HikitaNorio Hayashi
Feb 18, 2010·Molecular Cell·Jerry E ChipukDouglas R Green

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Citations

Oct 1, 2010·International Journal of Hematology·Maryse ProulxDaniel Jung
May 31, 2012·Nature Cell Biology·Joshua L Andersen, Sally Kornbluth
Feb 22, 2012·Genes & Development·Gregory J Gores, Scott H Kaufmann
Dec 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Toru OkamotoDavid C S Huang
Feb 5, 2013·Cold Spring Harbor Perspectives in Biology·J Marie Hardwick, Lucian Soane
Aug 8, 2015·International Journal of Molecular Sciences·Ewelina SynowiecJanusz Błasiak
Jan 22, 2013·Mitochondrion·Melanie A McNallyJ Marie Hardwick
Oct 3, 2012·Trends in Cell Biology·Rhonda M Perciavalle, Joseph T Opferman
May 9, 2012·Trends in Cell Biology·J Marie HardwickElizabeth A Jonas
Mar 13, 2013·EMBO Reports·Franziska ErtelGordon C Shore
Jul 17, 2015·Cell Biochemistry and Function·Curtis C HarnettEric R Gauthier
Mar 10, 2015·Trends in Endocrinology and Metabolism : TEM·Alfredo Giménez-Cassina, Nika N Danial
Apr 23, 2015·BMC Genomics·Lindsay M ReynoldsYongmei Liu
Feb 12, 2013·Molecular Cell·Joshua L Andersen, Sally Kornbluth
Jul 26, 2011·The Journal of Biological Chemistry·Hsin-Fang Yang-Yen
Feb 26, 2020·Cell Death and Differentiation·Tirta Mario DjajawiMark F van Delft
Nov 11, 2020·The Journal of Biological Chemistry·Hubert PengHsin-Fang Yang-Yen
Jan 8, 2021·The Journal of Biological Chemistry·Hubert PengHsin-Fang Yang-Yen
Sep 4, 2021·Communications Biology·Hayley Widden, William J Placzek

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