Artículo
Role of the lipid transport protein StarD7 in mitochondrial dynamics
Rojas, Maria Laura
; Cruz del Puerto, Mariano Matias Arzud
; Flores-Martín, Jésica; Racca, Ana Cristina
; Kourdova, Lucille Tihomirova
; Miranda, Andrea Lis
; Panzetta-Dutari, Graciela Maria del Valle
; Genti de Raimondi, Susana
Fecha de publicación:
12/2021
Editorial:
Elsevier Science
Revista:
Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids
ISSN:
1388-1981
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Mitochondria are dynamic organelles crucial for cell function and survival implicated in oxidative energy production whose central functions are tightly controlled by lipids. StarD7 is a lipid transport protein involved in the phosphatidylcholine (PC) delivery to mitochondria. Previous studies have shown that StarD7 knockdown induces alterations in mitochondria and endoplasmic reticulum (ER) with a reduction in PC content, however whether StarD7 modulates mitochondrial dynamics remains unexplored. Here, we generated HTR-8/SVneo stable cells expressing the precursor StarD7.I and the mature processed StarD7.II isoforms. We demonstrated that StarD7.I overexpression altered mitochondrial morphology increasing its fragmentation, whereas no changes were observed in StarD7.II-overexpressing cells compared to the control (Ct) stable cells. StarD7.I (D7.I) stable cells were able to transport higher fluorescent PC analog to mitochondria than Ct cells, yield mitochondrial fusions, maintained the membrane potential, and produced lower levels of reactive oxygen species (ROS). Additionally, the expression of Dynamin Related Protein 1 (Drp1) and Mitofusin (Mfn2) proteins were increased, whereas the amount of Mitofusin 1 (Mfn1) decreased. Moreover, transfections with plasmids encoding Drp1-K38A, Drp1-S637D or Drp1-S637A mutants indicated that mitochondrial fragmentation in D7.I cells occurs in a fission-dependent manner via Drp1. In contrast, StarD7 silencing decreased Mfn1 and Mfn2 fusion proteins without modification of Drp1 protein level. These cells increased ROS levels and presented donut-shape mitochondria, indicative of metabolic stress. Altogether our findings provide novel evidence indicating that alterations in StarD7.I expression produce significant changes in mitochondrial morphology and dynamics.
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Rojas, Maria Laura; Cruz del Puerto, Mariano Matias Arzud; Flores-Martín, Jésica; Racca, Ana Cristina; Kourdova, Lucille Tihomirova; et al.; Role of the lipid transport protein StarD7 in mitochondrial dynamics; Elsevier Science; Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids; 1866; 12; 12-2021; 1-11
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