Dynamin-1-like protein mRNA (DNM1L mRNA)

Dynamin-1-like protein (Drp1) mRNA encodes a cytosolic GTPase that serves as a master regulator of mitochondrial and peroxisomal fission (UniProt Consortium, 2023). In hepatocytes, Drp1 is recruited to the mitochondrial outer membrane to facilitate organelle division, a process essential for maintaining mitochondrial health and responding to metabolic demands (Galloway & Yoon, 2013). Pathological overexpression or hyperactivation of Drp1 in the liver is a hallmark of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), where it drives mitochondrial fragmentation, oxidative stress, and cell death (Zhan et al., 2022). Therapeutic strategies targeting Drp1 mRNA, such as antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), aim to selectively reduce Drp1 protein levels in hepatocytes to mitigate these pathological effects (Simões et al., 2020). By restoring the balance between mitochondrial fusion and fission, these interventions can improve hepatic insulin sensitivity and reduce lipid accumulation. While small molecule inhibitors like Mdivi-1 target the protein directly, mRNA-based approaches offer the potential for high specificity and long-lasting suppression of the fission machinery in the liver. This target is particularly relevant in the context of chronic liver diseases where mitochondrial dysfunction is a primary driver of disease progression.

Other names

Drp1 mRNADynamin-related protein 1 mRNADLP1 mRNADVLP mRNADYMPLE mRNAEMPPF1 mRNA

Reduction of Dynamin-1-like protein expression via mRNA degradation or translational repression, leading to the inhibition of excessive mitochondrial fission and restoration of mitochondrial network integrity.