TOM-independent complex formation of Bax and Bak in mammalian mitochondria during TNFalpha-induced apoptosis.
The Bcl-2 family proteins Bax and Bak are activated in response to many apoptotic stimuli. As a consequence of activation, Bax and Bak oligomerize and permeabilize the outer mitochondrial membrane to permit the release of apoptosis-inducing factors. It still remains unclear whether these proteins require components of the mitochondrial protein import machinery for their function at the mitochondria. Here, we addressed this question by using inducible RNA interference for the study of protein import in mammalian mitochondria. After induction of apoptosis, we could not detect any impact of the absence of Tom22, Tom70, Tom40, Sam50 or metaxins on the translocation of Bax and formation of Bax and Bak complexes in mitochondria. In in vitro import studies, loss of these import and assembly proteins had no or only slight effect on the formation of complexes by radiolabeled Bax and Bak. We conclude that the import and assembly machineries of mammalian mitochondria have no impact on the translocation and complex assembly of Bax and Bak upon apoptosis induction.
Ross
K
K
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
Rudel
T
T
Kozjak-Pavlovic
V
V
D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism; D034622:RNA Interference; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D002352:Carrier Proteins; D008565:Membrane Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; C522815:SAMM50 protein, human; D014409:Tumor Necrosis Factor-alpha; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D004318:Doxycycline