Yme1l1, a mitochondrial metalloproteinase, is an ATP-dependent protease located in the mitochondrial inner membrane. Its protease domain faces the mitochondrial intermembrane space and modulates the processing of the mitochondrial GTPase optic atrophy type 1 (OPA1), thus playing a crucial role in mitochondrial dynamics, biogenesis, and function. It is also involved in mitochondrial quality control, responding to protein import impairments and governing unoccupied protein translocase channels [4].

In Sirt3-related studies, Sirt3 deficiency exacerbates LPS-induced renal pathological damage, apoptosis, and mitochondrial function/dynamics disturbances in mice, while Sirt3 overexpression alleviates these lesions by promoting OPA1-mediated mitochondrial fusion through Yme1l1 deacetylation in renal tubular epithelial cells [1].

In porcine embryo development, knocking down Yme1l1 mRNA leads to decreased blastocyst rate and quality, mitochondrial fragmentation, excessive ROS production, lower mitochondrial membrane potential, and ATP levels, indicating its essential role in regulating mitochondrial fission, function, and apoptosis during pre-implantation development [2].

In T-cell memory development, SENP1-Sirt3 signalling reduces Yme1l1 acetylation, suppressing its OPA1-cleavage activity to facilitate mitochondrial fusion and promote T-cell memory development [3].

In conclusion, Yme1l1 is essential for maintaining mitochondrial function, including mitochondrial dynamics, energy metabolism, and apoptosis regulation. Gene-knockout or knockdown models in different organisms have revealed its significant roles in various biological processes and disease-related conditions such as acute kidney injury, porcine embryo development, and T-cell memory development. These studies provide valuable insights into understanding the mechanisms underlying mitochondrial-related functions and diseases.