Stable bioreactor control reveals acidic pH-driven metabolic reprogramming and mitochondrial dysfunction in human lymphoblastoid cells - PubMed
3 hours ago
- #acidic pH
- #mitochondrial dysfunction
- #metabolic reprogramming
- The study used a gas-only bioreactor to maintain controlled acidic pH conditions for human lymphoblastoid cells, revealing that acidic pH causes a shift towards glycolytic metabolism, reduces cell proliferation, and leads to lactate and oncometabolite accumulation.
- Acidic conditions resulted in mitochondrial dysfunction, increased reactive oxygen species (ROS), and activated inflammatory and immune pathways, while also promoting heteroplasmic enrichment of a pathogenic mitochondrial DNA mutation.
- Acidic pH depleted intracellular NAD⁺, partly due to PARP1 activation. Supplementation with nicotinamide mononucleotide (NMN) or inhibition of PARP1 restored NAD⁺ levels, partially rescued proliferation and stress responses, and reversed the heteroplasmic enrichment of mutant mitochondrial DNA.