Next, we applied MitoRFAP-2 to measure endogenous changes in mitochondrial FA pools in the SNU-182 hepatocellular carcinoma cell line expressing a very common human mutation in the mitochondrial ALDH2 enzyme, termed ALDH2*2. Individuals who express ALDH2*2 possess a single nucleotide polymorphism that results in an inactive E487K point mutant enzyme, in a homozygous or heterozygous manner. This population has a greatly reduced ability to metabolize acetaldehyde, the initial product of ethanol metabolism, as well as other endogenously produced aldehydes, including formaldehyde. This pervasive human mutation is associated with a flushing effect upon consumption of alcohol, a phenotypic signature of acetaldehyde build-up, and is connected to the development of cancer, 59,60 cardiovascular disease, 61 and neurodegenerative diseases. Using MitoRFAP-2 imaging, we probed whether a chronic, aberrantly-elevated aldehyde state could be modulated via pharmacological treatment with a small-molecule ALDH2 activator, Alda-1;