1. Biochemistry Section, SNB, NINDS, NIH, Bethesda, Maryland 20892, USA
2. †Present addresses: University of Maryland Biotechnology Institute, Medical Biotechnology Center, UMBI Building, 725 West Lombard Street, Baltimore, Maryland 21201, USA (M.K.); Department of Medical Genetics, School of Medicine, Ajou University, Suwon 443-721, Korea (S.-Y.J.)
3. *These authors contributed equally to this work

Correspondence to: Mariusz Karbowski^1,3,2Richard J. Youle¹ Correspondence and requests for materials should be addressed to M.K. or R.Y. (Email: karbowsm@ninds.nih.gov, Email: youler@ninds.nih.gov).

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.

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