Bcl-2 and porin follow different pathways of TOM-dependent insertion into the mitochondrial outer membrane.
The bcl-2 gene encodes a 26kDa protein which functions as a central regulator of apoptosis. Here we investigated the pathway of Bcl-2alpha into the mitochondrial outer membrane using the yeast Saccharomyces cerevisiae as a model organism. We found that interactions of Bcl-2alpha with the mitochondrial import receptor Tom20 are dependent on two positively charged lysine residues in the immediate vicinity of the carboxy-terminal hydrophobic membrane anchor. The targeting function of these residues is independent of Tom22. Subsequent insertion of Bcl-2alpha into the mitochondrial outer membrane does not require Tom5 or Tom40, indicating that Bcl-2alpha bypasses the general import pore (GIP). Bcl-2alpha shows a unique pattern of interactions with the components of the mitochondrial TOM complex, demonstrating that at least two different pathways lead from the import receptor Tom20 into the mitochondrial outer membrane.
Motz
Christian
C
Institut für Mikrobiologie, Universität Hohenheim, Garbenstr. 30, Stuttgart-Hohenheim, Germany.
Martin
Heiko
H
Krimmer
Thomas
T
Rassow
Joachim
J
D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D018272:Porins / Q000378:metabolism*; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D018272:Porins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; C489350:TOM20 protein, S cerevisiae; C090857:TOM22 protein, S cerevisiae; C084008:TOMM20 protein, human; C489971:TOMM22 protein, human; C489998:Tomm20 protein, rat; D050994:Voltage-Dependent Anion Channels; D008239:Lysine