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Basic Research Paper

A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes

, , , , &
Pages 1325-1332 | Received 09 May 2012, Accepted 15 May 2012, Published online: 21 Aug 2012
 

Abstract

Elimination of defective mitochondria is essential for the health of long-lived, postmitotic cells. To gain insight into this process, we examined programmed mitochondrial clearance in reticulocytes. BNIP3L is a mitochondrial outer membrane protein that is required for clearance. It has been suggested that BNIP3L functions by causing mitochondrial depolarization, activating autophagy, or engaging the autophagy machinery. Here we showed in mice that BNIP3L activity localizes to a small region in its cytoplasmic domain, the minimal essential region (MER). The MER is a novel sequence, which comprises three contiguous hydrophobic amino acid residues, and flanking charged residues. Mutation of the central leucine residue causes complete loss of BNIP3L activity, and prevents rescue of mitochondrial clearance. Structural bioinformatics analysis predicts that the BNIP3L cytoplasmic domain lacks stable tertiary structure, but that the MER forms an α-helix upon binding to another protein. These findings support an adaptor model of BNIP3L, centered on the MER.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors thank Stephane Pelletier for assistance with the immunofluorescent localization of FLAG-BNIP3L. The authors also thank the members of the Flow Cytometry Laboratory and the Animal Resource Center of St. Jude Children’s Research Hospital. Bax and Bak mutant mice were a gift of the Korsmeyer laboratory and Joseph Opferman. BclXfl/fl and Tg(MMTV-Cre) mutant mice were a gift of Lothar Henighausen. This work was supported by a grant from the National Institutes of Health, R21 DK074519 (P.A.N.), by the New York Blood Center, and by the American, Lebanese and Syrian Associated Charities.

Supplemental Materials

Supplemental materials may be found here: www.landesbioscience.com/journals/autophagy/article/20764

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