RT info:eu-repo/semantics/article
T1 Silencing of the Charcot–Marie–Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry
A1 Pla-Martín, David
A1 Rueda, Carlos B.
A1 Estela, Anna
A1 Sánchez-Piris, Maribel
A1 González-Sánchez, Paloma
A1 Traba, Javier
A1 de la Fuente, Sergio
A1 Scorrano, Luca
A1 Renau-Piqueras, Jaime
A1 Alvarez, Javier
A1 Satrústegui, Jorgina
A1 Palau, Francesc
AB GDAP1 is an outer mitochondrial membrane protein that acts as a regulator of mitochondrial dynamics. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth (CMT) neuropathy. We show that GDAP1 interacts with the vesicle-organelle trafficking proteins RAB6B and caytaxin, which suggests that GDAP1 may participate in the mitochondrial movement within the cell. GDAP1 silencing in the SH-SY5Y cell line induces abnormal distribution of the mitochondrial network, reduces the contact between mitochondria and endoplasmic reticulum (ER) and alters the mobilization of mitochondria towards plasma membrane upon depletion of ER-Ca(2+) stores. GDAP1 silencing does not affect mitochondrial Ca(2+) uptake, ER-Ca(2+), or Ca(2+) flow from ER to mitochondria, but reduces Ca(2+) inflow through store-operated Ca(2+) entry (SOCE) following mobilization of ER-Ca(2+) and SOCE-driven Ca(2+) entry in mitochondria. Our studies suggest that the pathophysiology of GDAP1-related CMT neuropathies may be associated with abnormal distribution and movement of mitochondria throughout cytoskeleton towards the ER and subplasmalemmal microdomains, resulting in a decrease in SOCE activity and impaired SOCE-driven Ca(2+) uptake in mitochondria.
PB elsevier
SN 0969-9961
YR 2013
FD 2013-07
LK https://uvadoc.uva.es/handle/10324/70087
UL https://uvadoc.uva.es/handle/10324/70087
LA eng
NO Pla-Martín D, Rueda CB, Estela A, Sánchez-Piris M, González-Sánchez P, Traba J, de la Fuente S, Scorrano L, Renau-Piqueras J, Alvarez J, Satrústegui J, Palau F. Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry. Neurobiol Dis. 2013 Jul;55:140-51. doi: 10.1016/j.nbd.2013.03.010. Epub 2013 Mar 28. PMID: 23542510.
NO Producción Científica
DS UVaDOC
RD 27-sep-2024