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.
Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / metabolism
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Apoptosis*
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Bcl-2-Like Protein 11
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HeLa Cells
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Humans
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Hydrophobic and Hydrophilic Interactions
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Membrane Proteins / metabolism
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Metalloendopeptidases / metabolism
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Mice
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Mitochondria / enzymology
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Mitochondria / metabolism*
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Mitochondrial Processing Peptidase
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Mutant Proteins / metabolism
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Myeloid Cell Leukemia Sequence 1 Protein
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Protein Binding
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Protein Isoforms / chemistry
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Protein Isoforms / metabolism
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Protein Processing, Post-Translational
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Protein Sorting Signals
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Protein Transport
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Sequence Deletion
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Subcellular Fractions / metabolism
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Tumor Suppressor Proteins / metabolism
Substances
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Mcl1 protein, mouse
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Membrane Proteins
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Mutant Proteins
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Myeloid Cell Leukemia Sequence 1 Protein
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PUMA protein, mouse
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Pmaip1 protein, mouse
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Protein Isoforms
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Protein Sorting Signals
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Proteins
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Metalloendopeptidases