Mitochondrial Dynamics: Functional Link with Apoptosis

Figure 1

Domain structure of Drp1 and schematic view of the regulation of Drp1 by posttranslational modifications. Drp1 activity is regulated by various posttranslational modifications and changes in these modifications are related to several disorders. Under oxidative stress, protein kinase Cδ (PKCδ) phosphorylates Drp1 at Ser616 in the GED domain. Drp1 is recruited to mitochondria and stimulates mitochondrial fission, leading to apoptosis in hypertension-induced brain. Cyclic-AMP-dependent protein kinase (PKA) phosphorylates Drp1 at Ser637 in the GED domain. This reaction releases Drp1 from mitochondria to the cytosol, leading to mitochondrial elongation and suppression of apoptosis vulnerability of the cells. Calcineurin dephosphorylates Drp1 at Ser637 and promotes mitochondrial fragmentation and cell vulnerability to apoptosis. Polyglutamine expansion in huntingtin protein activates calcineurin and increases mitochondrial fragmentation and cell vulnerability to apoptosis. β-Amyloid protein increases S-nitrosylation of Drp1 at Cys644 in the GED domain to trigger mitochondrial fission by activating GTPase, thereby causing synaptic loss. All amino acid numbering is based on the human Drp1 splice variant 1 sequence.