Year: 2015
Type: article
Abstract: Unlike other cellular components, the mitochondrion is a dynamic organelle that undergoes frequent fission (the process of dividing into two or more organelles) or fusion (the opposite effect). Regulation of mitochondrial shape and dynamics can have a bearing on the metabolic state of the cell, which in turn can affect proliferation. Cancers, including glioblastomas (GBMs), in general have higher rates of mitochondrial fission, but their status and regulation in brain tumor-initiating cells (BTICs) are poorly characterized. Using biochemical and pharmacological approaches in a study published in Nature Neuroscience, Xie et al delineate the mechanisms regulating mitochondrial dynamics in BTICs. They first discovered that BTICs display fragmented mitochondrial morphology compared with non-BTICs. Correspondingly, the mitochondrial fission-regulating GTPase, dynamin-related protein 1 (DRP1), was found to be differentially phosphorylated and hyperactivated in BTICs when compared with non-BTICs. Silencing DRP1 caused reduction of growth and neurosphere formation efficiency of BTICs, with an associated reduction in the expression of stem cell markers and tumor initiation in intracranial xenografts. These features were also observed when DRP1 was targeted using a small-molecule inhibitor of its GTPase activity (Mdivi-1), supporting the notion that DRP1 represents a novel target for GBM.
Source: Neuro-Oncology
Authors: Krishna P. Bhat, Sean E. Lawler, Whitney B. Pope, Jason T. Huse, Kenneth Aldape
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4251378770