PMID- 22906961 OWN - NLM STAT- MEDLINE DCOM- 20130116 LR - 20211021 IS - 1554-8635 (Electronic) IS - 1554-8627 (Print) IS - 1554-8627 (Linking) VI - 8 IP - 9 DP - 2012 Sep TI - A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. PG - 1325-32 LID - 10.4161/auto.20764 [doi] AB - 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 alpha-helix upon binding to another protein. These findings support an adaptor model of BNIP3L, centered on the MER. FAU - Zhang, Ji AU - Zhang J AD - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA. FAU - Loyd, Melanie R AU - Loyd MR FAU - Randall, Mindy S AU - Randall MS FAU - Waddell, M Brett AU - Waddell MB FAU - Kriwacki, Richard W AU - Kriwacki RW FAU - Ney, Paul A AU - Ney PA LA - eng GR - R21 DK074519/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120821 PL - United States TA - Autophagy JT - Autophagy JID - 101265188 RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Nix protein, mouse) RN - 0 (bcl-X Protein) RN - GMW67QNF9C (Leucine) SB - IM MH - Amino Acid Motifs MH - Amino Acid Sequence MH - Animals MH - Computational Biology MH - Hydrophobic and Hydrophilic Interactions MH - Leucine/metabolism MH - Membrane Proteins/*chemistry/deficiency/*metabolism MH - Mice MH - Mitochondria/*metabolism MH - Mitochondrial Proteins/*chemistry/deficiency/*metabolism MH - Molecular Sequence Data MH - Protein Structure, Tertiary MH - Reticulocytes/*metabolism MH - Structure-Activity Relationship MH - bcl-X Protein/metabolism PMC - PMC3442879 EDAT- 2012/08/22 06:00 MHDA- 2013/01/17 06:00 PMCR- 2013/09/01 CRDT- 2012/08/22 06:00 PHST- 2012/08/22 06:00 [entrez] PHST- 2012/08/22 06:00 [pubmed] PHST- 2013/01/17 06:00 [medline] PHST- 2013/09/01 00:00 [pmc-release] AID - 20764 [pii] AID - 2012AUTO0203 [pii] AID - 10.4161/auto.20764 [doi] PST - ppublish SO - Autophagy. 2012 Sep;8(9):1325-32. doi: 10.4161/auto.20764. Epub 2012 Aug 21.