Nuclear NADH lifetime correlates with mtDNA transcription and NAD+ biosynthesis gene induction. (A) Pseudocolored images mitochondrial NADH lifetime analysis using FLIM across cybrid heteroplasmy levels. (B) Quantification of nuclear NADH lifetimes (NAD+/NADH ratio) across cybrid heteroplasmy levels. (C) mRNA levels of key NAD+ de novo synthesis enzymes across cybrid heteroplasmy levels (AFMID, Arylformamidase; NADSYN1, NAD Synthetase 1 [rate-limiting]; HAAO, 3-hydroxyanthranilate 3,4-dioxygenase NMNAT1, Nicotinamide Nucleotide Adenylyltransferase 1). (D) mtDNA mRNA levels across cybrid heteroplasmy levels. Reproduced from ref. 7. (E) Parallel fluctuations of Nuclear NADH lifetime (black, left axis), normalized NADH synthesis mRNA levels (blue), and normalized mtDNA mRNA levels (red) across cybrid heteroplasmy levels; n = 3.