Reassessing the role of NAD as a prosurvival factor

Nicolas Preyat1, Oberdan Leo1

  • 1Laboratory of Immunobiology, Department of Molecular Biology, Université Libre de Bruxelles , Gosselies, Belgium.

Insights

Nicotinamide adenine dinucleotide (NAD(+)) availability influences cell death pathways. It inhibits apoptosis but promotes necroptosis, a pro-inflammatory cell death, highlighting its regulatory role in distinct cell death programs.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Immunology

Background:

  • Mechanisms governing programmed cell death decisions are not fully understood.
  • Nicotinamide adenine dinucleotide (NAD(+)) is a crucial metabolite involved in cellular metabolism.
  • NAD(+) has demonstrated opposing effects on apoptosis and necroptosis.

Purpose of the Study:

  • To investigate the role of NAD(+) availability in regulating cell death.
  • To elucidate how NAD(+) influences the balance between apoptosis and necroptosis.

Main Methods:

  • Analysis of NAD(+) levels in cellular models.
  • Assessment of apoptosis and necroptosis markers.
  • Manipulation of NAD(+) availability to observe effects on cell death pathways.

Main Results:

  • NAD(+) availability was identified as a critical factor in determining cell fate.
  • Increased NAD(+) levels were found to suppress apoptosis.
  • Conversely, NAD(+) promoted necroptosis, a pro-inflammatory form of regulated cell death.

Conclusions:

  • NAD(+) plays a dual role in regulating distinct cell death programs.
  • Cellular NAD(+) levels are a key determinant in the choice between apoptosis and necroptosis.
  • This finding offers insights into the control of inflammatory cell death.