Divide et Impera: Drp1-mediated Mitochondrial Fission in Glioma Malignancy

Yale J Biol Med. 2019 Sep 20;92(3):423-433. eCollection 2019 Sep.

Abstract

Mitochondria are pivotal organelles involved in vital cellular functions, including energy generation, reactive oxygen species and calcium signaling, as well as intermediate biosynthesis. They are dynamic organelles that adapt their shape, size, and distribution to changes in intracellular conditions, being able to divide, fuse, or move along the cell, processes known as mitochondrial dynamics. Mitochondrial dynamics are involved in cell division and migration, as well as maintenance of pluripotency in stem (non-differentiated) cells. Thus, its central role in carcinogenesis is not surprising. Particularly, mitochondrial dynamics have been found to be pivotal to the development of gliomas, a lethal group of tumors developed from glial cells, which are nervous system cells that provide support to neurons. Unfortunately, prognosis of glioma patients is poor, most of them do not survive more than five years after diagnosis. In this context, it is fundamental to understand the cellular mechanisms involved in this pathology, in order to develop an appropriate clinical approach. As previously mentioned, mitochondrial dynamics is central to glioma development, particularly, mitochondrial division (fission) and one of its central effectors, dynamin-related protein 1 (Drp1), have been observed to be enhanced in gliomas and involved in the maintenance of stem cells (which initiate and maintain the tumor), as well as in migration and invasiveness, being central to gliomagenesis. In this review, we discuss the findings on mitochondrial fission role in these processes, further, we analyze the potential use of Drp1 as a novel prognostic biomarker in glioma patients.

Keywords: Drp1; cancer; glioma; mitochondria; organelles; stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Dynamins / metabolism*
  • Glioma / metabolism*
  • Humans
  • Mitochondrial Dynamics*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology

Substances

  • Biomarkers, Tumor
  • Dynamins