Mitochondria are complex organelles where a variety of crucial processes required for correct regulation of cell physiology take place. It has long been known that under healthy conditions, mitochondria supply the cell with ATP produced by oxidative phosphorylation and participate in a variety of catabolic and anabolic pathways. During the last two decades it also became recognized that mitochondria play an essential role in apoptosis. Diverse apoptotic stimuli cause release of apoptogenic factors from mitochondria that ultimately lead to caspase activation. Mitochondria are highly dynamic organelles that undergo fusion and fission events to a differing degree depending on the physiological status of the cell and on environmental cues. Abnormalities in mitochondrial fusion have been causatively linked to human neuropathies such as Charcot-Marie-Tooth disease type 2A and Dominant Optic Atrophy, while defects in mitochondrial fission have been implicated in Parkinson’s disease and Alzheimer’s disease. Mitochondrial morphological dynamics are mainly regulated by dynamin-related GTPases, a group of proteins with the intrinsic capacity to reorganize membrane structure in a oligomerization- and GTP hydrolysis-dependent manner leading to structural reorganization of the mitochondrial membranes. In mammals the dynamin-related GTPases implicated in mitochondrial fusion are the inner membrane protein Optic atrophy 1 and the outer membrane proteins mitofusins 1 and 2 . On the other hand, mitochondrial fission relies on Drp1, which is also involved in peroxisome division. Ablation of Drp1 function in mice has revealed the importance of this protein for correct development of the embryonic brain and other tissues. Importantly, dynamin-related GTPases also play an essential role in the normal progression of apoptosis. In this regard, we have shown that Drp1 stimulates Bax ICI 182780 129453-61-8 oligomerization and cytochrome c release by promoting tethering and hemifusion of mitochondrial membranes. In addition, in healthy cells Opa1 has been shown to assemble into high-order oligomers to maintain the architecture of the mitochondrial cristae, while during apoptosis, Opa1 oligomers disassemble to allow effective release of cytochrome c. Drp1 shows a four-domain architecture composed of the GTPase domain, the bundle signaling element implicated in the transmission of conformational changes from the G domain to the stalk, a so-called B insert implicated in regulation of Drp1 function and the stalk implicated in Drp1 multimerization. Inactive Drp1 is predominantly cytosolic, although a subpool of the protein concentrates in specific patches on mitochondria at sites of future fission, presumably where endoplasmic reticulum tubules contact mitochondria. Different aspects of Drp1 function, including its localization, stability, and GTPase activity have been reported to be regulated by posttranslational modifications such as phosphorylation, SUMOylation, ubiquitination, O-linked-N-acetylglucosamine glycosylation, and S-nitrosylation.