Dnm1l-flox Mouse

Dnm1l, also known as Dynamin-1-like protein (DRP1), is a key dynamin-related GTPase. It plays a crucial role in mitochondrial and peroxisomal fission, a process that is essential for maintaining mitochondrial quality control, cell metabolism, and apoptosis regulation. Mitochondrial fission is a highly regulated process, and Dnm1l is at the center of the machinery that drives the scission of mitochondria [3,5].

In glioblastoma, BCL2L13 targets Dnm1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux, which in turn promotes the proliferation and invasion of GBM cells [1]. Targeting the DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling [2]. Moreover, mutations in the Dnm1L gene, such as the R403C variant, can cause mitochondrial fission dysfunction, leading to severe neurological phenotypes like refractory status epilepticus, development regression, and brain atrophy [4].

In conclusion, Dnm1l is vital for mitochondrial fission and related cellular processes. Its dysregulation is associated with diseases, especially neurological disorders and glioma. Studies on Dnm1l, including those using gene-knockout models (implicit in understanding the impact of mutations as a form of functional loss), have provided insights into the molecular mechanisms underlying these disease conditions, potentially paving the way for new therapeutic strategies.