Role of the lipid transport protein StarD7 in mitochondrial dynamics

ROJAS, MARÍA L.; CRUZ DEL PUERTO, MARIANO; FLORES MARTIN, JESICA B.; MIRANDA ANDREA; KOURDOVA LUCILLE; PANZETTA-DUTARI, GRACIELA M.; GENTI-RAIMONDI, SUSANA

Simposio; Virtual live Keystone Symposia e Symposia meeting Lipidomics of Health and Disease; 2021

Mitochondria are dynamics organelles crucial for cell function and survival implicatedin oxidative energy production. Mitochondrial lipids affect several important functionssuch as respiratory metabolism, membrane architecture, protein import, mitophagy andmitochondrial dynamics. StarD7 is a lipid transport protein that carriesphosphatidylcholine (PC) to the mitochondria. Among the proteins responsible formaintaining mitochondrial dynamics, Mitofusin 1, 2 (Mfn1 and Mfn2) and Opticatrophy type-1 (Opa1) are involved in fusion process while Dynamin-related protein 1(Drp1) and Fission 1 (Fis1) participate in mitochondrial fission. Previous studies haveshown that StarD7 knockdown induces alterations in mitochondria and endoplasmicreticulum morphology with a reduction in mitochondrial PC content, however howdifferent StarD7 levels affect the mitochondrial dynamics was unexplored. Here, wegenerated HTR8/SVneo stable cell lines expressing the mitochondrial -StarD7.I- and thecytosolic -StarD7.II- isoforms. We demonstrated that StarD7.I overexpression promotesaltered mitochondrial morphology whereas no changes were observed in stableStarD7.II cells regarding control cells. These data were confirmed byimmunofluorescence analysis in HTR-8/SVneo wild type cells transiently transfectedwith the bicistronic p-Lenti-StarD7.I-IRES-EGFP and p-Lenti-StarD7.II-IRES-EGFPplasmids. Stable StarD7.I cells increase the expression of Drp1 and Mfn2 proteins, incontrast the levels of Mfn1 were decreased and no changes were observed in PGC1αprotein levels. Moreover, transfections with plasmids encoding Drp1-K38A, Drp1-S637D or Drp1-S637A mutants indicated that mitochondrial fragmentation in StarD7.Istable cells occurs in a fission-dependent manner via Drp1. Finally, the StarD7 silencedcells led to mitochondrial fragmentation with a donut phenotype, associated to higherROS levels. Altogether these findings indicate that alterations in StarD7.I expressionproduce significant changes in proteins that control the mitochondrial morphologyimpacting in mitochondrial dynamics. Granted by FONCyT, SECyT-UNC.