MTD-like motif of a BH3-only protein, BNIP1, induces necrosis accompanied by an intracellular calcium spike

Biochem Biophys Res Commun. 2018 Jan 8;495(2):1661-1667. doi: 10.1016/j.bbrc.2017.12.022. Epub 2017 Dec 5.

Abstract

The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity when conjugated with cell-penetrating peptide (CPP). In this study, we report another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with CPP, induced necrosis in a way similar to that of R8:MTD. R8:B1MLM caused an intracellular calcium spike, mitochondrial reactive oxygen species generation, and mitochondrial fragmentation. The cytosolic calcium spike was likely due to the opening of the mitochondrial permeability transition pore.

Keywords: B1MLM; BNIP1; MTD; NOXA; Necrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Calcium Signaling*
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / metabolism
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Necrosis
  • Proto-Oncogene Proteins c-bcl-2 / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • BNIP1 protein, human
  • Cell-Penetrating Peptides
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species