title: Role of Bax and Bak in mitochondrial morphogenesis.
abstract: Bcl-2 family proteins are potent regulators of programmed cell death. Although their intracellular localization to mitochondria and the endoplasmic reticulum has focused research on these organelles, how they function remains unknown. Two members of the Bcl-2 family, Bax and Bak, change intracellular location early in the promotion of apoptosis to concentrate in focal clusters at sites of mitochondrial division. Here we report that in healthy cells Bax or Bak is required for normal fusion of mitochondria into elongated tubules. Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility-properties that correlate with different GTP-bound states of Mfn2. Our results show that Bax and Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2 family members may also regulate apoptosis through organelle morphogenesis machineries.
authors.affiliation: Biochemistry Section, SNB, NINDS, NIH, Bethesda, Maryland 20892, USA. karbowsm@ninds.nih.gov
authors.forename: Mariusz
authors.initials: M
authors.lastname: Karbowski
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Norris
authors.forename: Megan M
authors.initials: MM
authors.lastname: Cleland
authors.forename: Seon-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Youle
mesh_terms: D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D009024:Morphogenesis; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse