Serine 39 in the GTP‐binding domain of Drp1 is involved in shaping mitochondrial morphology

Autor: Marvi Ghani, Bernadett Szabó, Mahmoud Alkhatibe, Hailemariam Amsalu, Peleg Zohar, Eszter Anna Janka, János András Mótyán, Krisztina Tar
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: FEBS Open Bio, Vol 14, Iss 7, Pp 1147-1165 (2024)
Druh dokumentu: article
ISSN: 2211-5463
DOI: 10.1002/2211-5463.13820
Popis: Continuous fusion and fission are critical for mitochondrial health. In this study, we further characterize the role played by dynamin‐related protein 1 (Drp1) in mitochondrial fission. We show that a single amino acid change in Drp1 at position 39 from serine to alanine (S39A) within the GTP‐binding (GTPase) domain results in a fused mitochondrial network in human SH‐SY5Y neuroblastoma cells. Interestingly, the phosphorylation of Ser‐616 and Ser‐637 of Drp1 remains unaffected by the S39A mutation, and mitochondrial bioenergetic profile and cell viability in the S39A mutant were comparable to those observed in the control. This leads us to propose that the serine 39 residue of Drp1 plays a crucial role in mitochondrial distribution through its involvement in the GTPase activity. Furthermore, this amino acid mutation leads to structural anomalies in the mitochondrial network. Taken together, our results contribute to a better understanding of the function of the Drp1 protein.
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