dc.contributor.advisor	Tar, Krisztina
dc.contributor.author	Ghani, Marvi
dc.contributor.department	Molekuláris orvostudomány doktori iskola	hu
dc.date.accessioned	2025-02-06T13:41:48Z
dc.date.available	2025-02-06T13:41:48Z
dc.date.defended	2025-02-27
dc.date.issued	20250227
dc.description.abstract	The study explored the impact of DRP1, an essential protein in splitting mitochondria, on differentiating SH-SY5Y cells into neurons. Decreasing the DRP1 levels led to a reorganization of the mitochondrial network and an increase in the expression of genes related to neuronal development, such as synapse formation, neurogenesis, differentiation, and morphogenesis. The reduction of DRP1 enhanced neuronal differentiation, resulting in longer neurite outgrowth, improved number of segments, and more branch points. Neuronal differentiation induced by RA-BDNF was accompanied by a notable decrease in ERK1/2 phosphorylation, indicating an ERK1/2 independent pathway for neuronal differentiation in shDrp1 cells. Additionally, there was no influence from dual specificity phosphatases DUSP1/6 on the phosphorylation status of ERK1/2 in shDrp1 cells, which maintained highly fused and elongated mitochondrial structures during differentiation while displaying significantly elevated maximal respiration. These findings suggest that lowering DRP1 promotes neuronal maturation through genomic and mitochondria rearrangement in undifferentiated cells. Regarding apoptosis or cell death, the shDrp1 reacted similarly to control when examined in vitro. Several crucially toxic aggregates associated with mutant huntingtin protein (mHtt) were notably reduced following the overexpression within these shDrp1 cells. This implies that lowering DRP1 in a regulated manner can increase several parameters, such as cell viability, neurotoxicity, and cellular bioenergetics. In conclusion, the research findings have shed light on the multifaceted roles of DRP1 in neuronal function. Further research is needed to investigate the mechanisms that can be very helpful in identifying therapeutic targets to treat neurodegenerative diseases. DRP1 and its function in the GTPase domain are essential for morphology and cellular respiration. S39A mutation of DRP1 caused elongated, fused, and clustered tubular mitochondria compared to normal cells. Despite these changes, the energy remained unchanged, and cell death was reduced in the S39A mutant compared to those with the wild-type DRP1. These findings suggest that S39 plays a crucial role in distributing mitochondria within a cell by regulating GTPase activity and that mutations at this site cause structural abnormalities in the mitochondrial network. This study contributes new insight into understanding how DRP1 functions.
dc.format.extent	152
dc.identifier.uri	https://hdl.handle.net/2437/386845
dc.language.iso	en
dc.subject	Mitochondrial dynamics, Dynamin protein 1/DRP1, Mitochondria morphology, Mitofusin and Opa1, Neurodegeneration, Neuronal differentiation, RA-BDNF differentiation, SH-SY5Y human neuroblastoma cells, Neuronal markers genes, ERK1/2, MAPK signaling, DUSP1/6 and DRP1 mutations.
dc.subject.discipline	Elméleti orvostudományok	hu
dc.subject.sciencefield	Orvostudományok	hu
dc.title	The role of DRP1-a mitochondrial fission protein- in mitochondrial morphology rearrangement during neuronal differentiation
dc.title.translated	A DRP1 - a mitokondriális hasadási fehérje - szerepe a mitokondriális morfológiai átrendeződésben a neuronális differenciálódás során
dc.type	PhD, doktori értekezés	hu

The role of DRP1-a mitochondrial fission protein- in mitochondrial morphology rearrangement during neuronal differentiation

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