Purine levels affect survival of cells lacking energy complex I when relying on oxidative energy production

Supplementation with adenosine monophosphate (AMP) improves cell viability in fibroblasts relying on oxidative phosphorylation.

• Growing fibroblasts in galactose instead of glucose enhances their dependence on oxidative phosphorylation for energy.
• Nicotinamide adenine dinucleotide (NAD⁺) treatment improves the viability of human fibroblasts deficient in OXPHOS Complex I.
• While various NAD⁺ precursors showed no improvement in cell viability, niacin partially improved it.
• Only adenosine and guanosine treatments increased patient cell viability in OXPHOS-reliant conditions.
• Increased levels of inosine monophosphate (IMP) were associated with improved cell viability when AMP and adenosine were supplemented.
• The OXPHOS-reliant condition may limit purine nucleotide biosynthesis and salvage pathways, which could be targeted for therapeutic intervention.

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