Title:Drp1 in Ischemic Neuronal Death: An Unusual Suspect
Volume: 21
Issue: 19
Author(s): H. Pradeep, B. Sharma and G.K. Rajanikant
Affiliation:
Keywords:
Cerebral ischemia, mitochondrial fission, dynamin related protein 1, apoptosis.
Abstract: Mitochondria play a crucial role in multitude of cellular processes including energy production, calcium signaling,
and apoptosis. This remarkable organelle constantly undergoes a complex cycle of fusion and fission, a crucial quality
control system for maintaining homeostasis of the cell. Any impairment in this dynamic behavior is linked to a wide range
of cellular abnormalities. Consistent with this concept, neuronal apoptosis often emanates in conjunction with rampant mitochondrial
fragmentation. The mitochondrial dynamics are tightly regulated by a master mediator called Dynamin related
protein 1 (Drp1), which in normal conditions facilitates mitochondrial fission. However, diverse stress conditions induce
intensified translocation of cytosolic Drp1 to the mitochondria, contributing excessive fragmentation and concomitant
apoptosis. Despite this knowledge, crucial questions such as how fission of the inner and outer mitochondrial membranes
is coordinated and how these processes are linked to apoptosis and necrosis remain to be answered. This review focuses
on delineating the mechanism of Drp1 activation and explores the pathophysiological importance of dysregulated mitochondrial
fission with a special emphasis on ischemic stroke. Further, it also provides a new mechanistic link between
ischemia and Drp1-mediated mitochondrial fission.
