A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes.
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.
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ji
J
Zhang
Melanie R
MR
Loyd
Mindy S
MS
Randall
M Brett
MB
Waddell
Richard W
RW
Kriwacki
Paul A
PA
Ney
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D057927:Hydrophobic and Hydrophilic Interactions; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012156:Reticulocytes / Q000378:metabolism*; D013329:Structure-Activity Relationship; D051020:bcl-X Protein / Q000378:metabolism
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C501741:Nix protein, mouse; D051020:bcl-X Protein; D007930:Leucine