Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis.
We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1K38A, inhibits apoptotic scission of mitochondria, but does not inhibit Bax translocation or coalescence into foci. However, Drp1K38A causes the accumulation of mitochondrial fission intermediates that are associated with clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci. We suggest that Bax participates in apoptotic fragmentation of mitochondria.
Karbowski
Mariusz
M
Biochemistry Section, SNB, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Lee
Yang-Ja
YJ
Gaume
Brigitte
B
Jeong
Seon-Yong
SY
Frank
Stephan
S
Nechushtan
Amotz
A
Santel
Ansgar
A
Fuller
Margaret
M
Smith
Carolyn L
CL
Youle
Richard J
RJ
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D020558:GTP Phosphohydrolases; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D013347:Subcellular Fractions; D013997:Time Factors; D014162:Transfection; D049411:Utrophin; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D049411:Utrophin; D051028:bcl-2-Associated X Protein; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human