Tufm, also known as mitochondrial Tu translation elongation factor, is a nuclear-encoded mitochondrial protein crucial for mitochondrial protein translation. It is evolutionarily conserved from prokaryotes to eukaryotes. Tufm is involved in pathways such as mitochondrial DNA translational expression and repair, mitophagy, and programmed cell death processes like apoptosis, necroptosis, and pyroptosis [2]. It also plays a role in various disease-related processes, including viral infection, cancer, and neurodegenerative diseases [2].

In multiple disease models, Tufm has shown significant impacts. In doxorubicin-induced cardiotoxicity, FUNDC1 interacts with Tufm to stabilize mtDNA and protect against cardiomyocyte PANoptosis [1]. In traumatic brain injury, Tufm lactylation at K286 inhibits its interaction with Tomm40, suppressing mitophagy and increasing neuronal apoptosis, while a lactylation-deficient TufmK286R mutant in mice rescues these effects [3]. In non-alcoholic steatohepatitis, MRG15 deacetylates Tufm, leading to its accelerated degradation by the mitochondrial ClpXP protease system, impaired mitophagy, and disease progression [4].

In conclusion, Tufm is essential for mitochondrial function and is intricately involved in disease-related processes. Gene knockout or conditional knockout mouse models have been instrumental in uncovering its role in cardiotoxicity, traumatic brain injury, and non-alcoholic steatohepatitis, providing insights into potential therapeutic targets for these diseases.