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

Ji Zhang, Melanie R. Loyd, Mindy S. Randall, M. Brett Waddell, Richard W. Kriwacki, Paul A. Ney

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1325-1332
Number of pages8
JournalAutophagy
Volume8
Issue number9
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Reticulocytes
Autophagy
Computational Biology
Leucine
Mitochondria
Membrane Proteins
Amino Acids
Mutation
Health
Proteins

Keywords

  • Autophagy
  • Mitophagy
  • NIX
  • Reticulocyte
  • SLiM

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Zhang, J., Loyd, M. R., Randall, M. S., Waddell, M. B., Kriwacki, R. W., & Ney, P. A. (2012). A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. Autophagy, 8(9), 1325-1332. https://doi.org/10.4161/auto.20764

A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. / Zhang, Ji; Loyd, Melanie R.; Randall, Mindy S.; Waddell, M. Brett; Kriwacki, Richard W.; Ney, Paul A.

In: Autophagy, Vol. 8, No. 9, 01.01.2012, p. 1325-1332.

Research output: Contribution to journalArticle

Zhang, J, Loyd, MR, Randall, MS, Waddell, MB, Kriwacki, RW & Ney, PA 2012, 'A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes', Autophagy, vol. 8, no. 9, pp. 1325-1332. https://doi.org/10.4161/auto.20764
Zhang, Ji ; Loyd, Melanie R. ; Randall, Mindy S. ; Waddell, M. Brett ; Kriwacki, Richard W. ; Ney, Paul A. / A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes. In: Autophagy. 2012 ; Vol. 8, No. 9. pp. 1325-1332.
@article{110b6ac9b3db402e96475127516467f8,
title = "A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes",
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.",
keywords = "Autophagy, Mitophagy, NIX, Reticulocyte, SLiM",
author = "Ji Zhang and Loyd, {Melanie R.} and Randall, {Mindy S.} and Waddell, {M. Brett} and Kriwacki, {Richard W.} and Ney, {Paul A.}",
year = "2012",
month = "1",
day = "1",
doi = "10.4161/auto.20764",
language = "English (US)",
volume = "8",
pages = "1325--1332",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes

AU - Zhang, Ji

AU - Loyd, Melanie R.

AU - Randall, Mindy S.

AU - Waddell, M. Brett

AU - Kriwacki, Richard W.

AU - Ney, Paul A.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

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 α-helix upon binding to another protein. These findings support an adaptor model of BNIP3L, centered on the MER.

KW - Autophagy

KW - Mitophagy

KW - NIX

KW - Reticulocyte

KW - SLiM

UR - http://www.scopus.com/inward/record.url?scp=84866543686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866543686&partnerID=8YFLogxK

U2 - 10.4161/auto.20764

DO - 10.4161/auto.20764

M3 - Article

VL - 8

SP - 1325

EP - 1332

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 9

ER -