Kmo, known as kynurenine-3-monooxygenase, is a mitochondrial enzyme. It is a key rate-limiting enzyme in the eukaryotic kynurenine pathway (KP), the major catabolic route of tryptophan. Kmo can convert kynurenine into the neurotoxin 3-hydroxykynurenine and quinolinic acid, which promotes the production of toxic metabolites and free radicals in the blood while reducing the neuroprotective metabolite kynurenic acid [1].

Inhibition of Kmo has shown beneficial effects in several disease models. In myocardial ischemia (MI) mice, Kmo was found to be highly elevated and was associated with the elevation of xanthurenic acid (XA) which induced myocardial injury. Pharmacological or heart-specific inhibition of Kmo suppressed XA elevation, ameliorated OGD-induced cardiomyocyte injury and ligation-induced MI injury by maintaining mitochondrial fusion and fission balance [2]. In unstable atherosclerotic plaque, Kmo was identified as a key gene. Lentivirus-mediated Kmo silencing in high-fat-fed ApoE-/-mice attenuated plaque formation and promoted plaque stability [3]. Also, in a stroke mouse model, circSCMH1 suppressed Kmo expression, enhancing mitochondrial fusion and inhibiting mitophagy to promote post-stroke brain repair [4].

In conclusion, Kmo plays a crucial role in the kynurenine pathway, influencing the production of neurotoxic and neuroprotective metabolites. Studies using gene-knockout or conditional-knockout mouse models have revealed its significance in diseases such as myocardial ischemia, atherosclerotic plaque instability, and stroke, suggesting that targeting Kmo could potentially be a new approach for treating these diseases.