ALKBH7, an AlkB homolog, is a mitochondrial α -ketoglutarate dioxygenase. It has essential functions in regulating mitochondrial polycistronic RNA processing as an RNA demethylase, specifically demethylating m22G and m1A within mitochondrial Ile and Leu1 pre -tRNA regions in nascent polycistronic mitochondrial RNA [1]. It is also involved in regulating dialdehyde metabolism, impacting the cardiac response to ischemia -reperfusion injury [2]. Additionally, it has been linked to programmed necrosis, tissue -and sex -specific necrotic cell death responses, and is associated with prostate cancer [3,4].

Alkbh7 -/- mice show elevated glyoxalase I, rewired metabolic pathways related to methylglyoxal, and increased resistance to MMS -induced toxicity in male mice [2,3]. Depletion of ALKBH7 in cells leads to increased polycistronic mitochondrial RNA processing, reduced steady -state mitochondria -encoded tRNA levels and protein translation, and decreased mitochondrial activity [1]. Knockdown of ALKBH7 in cell lines results in upregulation of UQCRH and HMGN1 expression [5].

In conclusion, ALKBH7 plays crucial roles in mitochondrial RNA processing, dialdehyde metabolism, and programmed necrosis. Studies using Alkbh7 knockout mouse models have revealed its functions in cardiac ischemia -reperfusion injury, tissue -and sex -specific necrotic cell death, and its potential association with prostate cancer, providing insights into disease mechanisms and potential therapeutic targets.