Physiological and Pathological Significance of Dynamin-Related Protein 1 (Drp1)-Dependent Mitochondrial Fission in the Nervous System

Abstract

Mitochondria are essential for proper neuronal morphogenesis and functions, as they are the major source of energy for neural development. The dynamic morphology of mitochondria determines the key functions of mitochondria. Several regulatory proteins such as dynamin-related protein 1 (Drp1) are required to maintain mitochondrial morphology via a balance between continuous fusion and fission. Activity of Drp1, a key regulator in mitochondrial fission, is modulated by multiple post-translation modifications and receptor interactions. In addition, numerous researches have revealed that the regulation of Drp1 activity and mitochondrial dynamics is closely associated with several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. In this article, we concisely review the recent findings about the biological importance of Drp1-mediated mitochondrial fission in neurons under physiological and pathological conditions.

Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington’s disease knock-in striatal cells

“…Drp1 is a cytosolic protein that translocates to the outer mitochondrial membrane to promote mitochondrial fragmentation. Phosphorylation of Drp1 at Ser616 is a target of several kinases, including Erk1/2, and was shown to enhance Drp1 activity, resulting in mitochondrial fragmentation [64]. In order to verify if Drp1 is actively increased in mutant cells, we measured the levels of p-(Ser616)Drp1…”

Mitochondrial dynamics in neuronal injury, development and plasticity

“…Perturbations in mitochondrial dynamics, and altered expression and activity of fission and fusion enzymes has been observed in almost every major neurodegenerative disorder (Table 1), yet it remains unclear precisely how alterations in mitochondrial dynamics contribute to the pathology of these diseases (DuBoff et al, 2013;Hroudová et al, 2014;Reddy et al, 2011;Yu-Wai-Man et al, 2011;Cho et al, 2013;Büeler, 2009). Furthermore, the importance of mitochondrial dynamics has been documented in neuronal development (Li et al, 2004;Dickey and Strack, 2011;Chan, 2006;Ishihara et al, 2009) and survival Merrill et al, 2013;Dagda et al, 2008;Merrill et al, 2011;Cho et al, 2010;Nakamura et al, 2010).…”

Melatonin attenuates the mitochondrial translocation of mitochondrial fission proteins and Bax, cytosolic calcium overload and cell death in methamphetamine-induced toxicity in neuroblastoma SH-SY5Y cells

“…Fis1 is a small protein that is located on the outer mitochondrial membrane (OMM), whereas Drp1 is primarily localized in the cytosol. Mitochondrial fission is predominantly controlled by the activity of Drp1; Drp1 translocates from the cytosol to the OMM and divides a mitochondrion into two pieces via GTP hydrolysis (Cho et al, 2013). Mitochondrial fusion is two-step processes that require outer and inner membrane fusion.…”