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

作者：Zhang Ji; Loyd Melanie R; Randall Mindy S; Waddell M Brett; Kriwacki Richard W; Ney Paul A^*

来源：Autophagy, 2012, 8(9): 1325-1332.

DOI：10.4161/auto.20764

• mitophagy
• NIX
• reticulocyte
• SLiM
• autophagy

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.

• 出版日期2012-9
• 单位上海生物信息技术研究中心