Isoform 6 of Dynamin-1-like protein

Dynamin-1-like protein (DNM1L), encoded by the DNM1L gene, is a GTPase that functions in mitochondrial fission and membrane dynamics (UniProt: O00429-6). This isoform 6 variant (749 amino acids, ~83 kDa) localizes to mitochondria where it participates in the regulated scission of mitochondrial tubules, a process critical for energy metabolism and cellular stress responses. DNM1L is broadly expressed across tissues including the central nervous system.

DNM1L is implicated in neurodegenerative pathways through its role in mitochondrial quality control. Impaired mitochondrial fission has been associated with neuronal dysfunction and cell death in various brain disorders, including those characterized by bioenergetic compromise. The protein's involvement in mitochondrial dynamics makes it relevant to pathways dysregulated in neuroinflammation and neurodegeneration.

In Alzheimer's Disease, this isoform is significantly downregulated in post-mortem brain tissue compared to age-matched controls (mean log2 fold-change: −1.09; Chaparral AD proteomics). This reduction may reflect compromised mitochondrial dynamics in AD neurons, potentially contributing to the bioenergetic deficits and accumulation of damaged mitochondria observed in the disease. The downregulation suggests impaired mitochondrial fission capacity in affected brain tissue.