A 20/20 view of ANT function in mitochondrial biology and necrotic cell death

J Mol Cell Cardiol. 2020 Jul:144:A3-A13. doi: 10.1016/j.yjmcc.2020.05.012. Epub 2020 May 23.

Abstract

The adenosine nucleotide translocase (ANT) family of proteins are inner mitochondrial membrane proteins involved in energy homeostasis and cell death. The primary function of ANT proteins is to exchange cytosolic ADP with matrix ATP, facilitating the export of newly synthesized ATP to the cell while providing new ADP substrate to the mitochondria. As such, the ANT proteins are central to maintaining energy homeostasis in all eukaryotic cells. Evidence also suggests that the ANTs constitute a pore-forming component of the mitochondrial permeability transition pore (MPTP), a structure that forms in the inner mitochondrial membrane that is thought to underlie regulated necrotic cell death. Additionally, emerging studies suggest that ANT proteins are also critical for mitochondrial uncoupling and for promoting mitophagy. Thus, the ANTs are multifunctional proteins that are poised to participate in several aspects of mitochondrial biology and the greater regulation of cell death, which will be discussed here.

Keywords: ANT; ATP; Heart; Mitochondria; Necrotic cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Mitochondrial ADP, ATP Translocases / genetics*
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore / metabolism
  • Models, Biological
  • Multigene Family
  • Necroptosis* / genetics
  • Oxidative Phosphorylation

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial ADP, ATP Translocases