Kmo, known as kynurenine-3-monooxygenase, is a mitochondrial enzyme. It is involved in the eukaryotic kynurenine pathway (KP), the major catabolic route of tryptophan. Kmo converts kynurenine into the neurotoxin 3-hydroxykynurenine and quinolinic acid, influencing the balance of toxic and neuroprotective metabolites in the KP [1].

In a MI mouse model, Kmo was found to be profoundly increased, and its elevation was associated with the induction of myocardial injury by promoting apoptosis and ferroptosis. Pharmacological or heart-specific inhibition of Kmo ameliorated OGD-induced cardiomyocytes injury and ligation-induced MI injury, suggesting that targeting Kmo may provide a new approach for MI treatment through maintaining mitochondrial fusion and fission balance [2].

In atherosclerotic plaque studies, Kmo was identified as a mitochondria-targeted gene associated with macrophage cells. Lentivirus-mediated KMO silencing in high-fat-fed ApoE-/-mice attenuated plaque formation and promoted plaque stability, indicating its potential as a biomarker for assessing plaque instability [3].

In stroke mouse models, circSCMH1 promoted post-stroke brain repair by suppressing Kmo expression, enhancing mitochondrial fusion, and inhibiting mitophagy [4].

In conclusion, Kmo plays a crucial role in the kynurenine pathway, influencing the production of various metabolites. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in diseases such as myocardial ischemia, atherosclerotic plaque instability, and stroke, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Chen, Yanmei, Zhang, Jiahui, Yang, Yueying, Sun, Dejuan, Chen, Lixia. 2022. Kynurenine-3-monooxygenase (KMO): From its biological functions to therapeutic effect in diseases progression. In Journal of cellular physiology, 237, 4339-4355. doi:10.1002/jcp.30876. https://pubmed.ncbi.nlm.nih.gov/36088660/

2. Lai, Qiong, Wu, Lingling, Dong, Shuhong, Yu, Boyang, Li, Fang. 2023. Inhibition of KMO Ameliorates Myocardial Ischemia Injury via Maintaining Mitochondrial Fusion and Fission Balance. In International journal of biological sciences, 19, 3077-3098. doi:10.7150/ijbs.83392. https://pubmed.ncbi.nlm.nih.gov/37416768/

3. Liao, Fu-Jun, Shen, Shao-Liang, Bao, Hai-Long, Li, Wei, Liu, Da-Nan. 2024. Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque. In Journal of translational medicine, 22, 668. doi:10.1186/s12967-024-05464-5. https://pubmed.ncbi.nlm.nih.gov/39026250/

4. Wang, Yu, Bai, Ying, Cai, Yang, Han, Bing, Yao, Honghong. 2024. Circular RNA SCMH1 suppresses KMO expression to inhibit mitophagy and promote functional recovery following stroke. In Theranostics, 14, 7292-7308. doi:10.7150/thno.99323. https://pubmed.ncbi.nlm.nih.gov/39659575/