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Reassessing the role of NAD as a prosurvival factor
1Laboratory of Immunobiology, Department of Molecular Biology, Université Libre de Bruxelles , Gosselies, Belgium.
Abstract:
The mechanisms regulating the choice of cell demise remain largely unknown. NAD(+), a key metabolite with well-known roles in cell metabolism, has been shown to counteract apoptosis while promoting necroptosis, a form of proinflammatory cell death. This observation identifies NAD(+) availability as an important parameter with contrasting roles in the regulation of distinct regulated cell death programs.
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.

