Role of the lipid transport protein StarD7 in mitochondrial dynamics

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2021-12, Vol.1866 (12), p.159029-159029, Article 159029
• Main Authors: Rojas, María L., Cruz Del Puerto, Mariano M., Flores-Martín, Jésica, Racca, Ana C., Kourdova, Lucille T., Miranda, Andrea L., Panzetta-Dutari, Graciela M., Genti-Raimondi, Susana
• Format: Article
• Language: English
• Subjects: Carrier Proteins - genetics; Dynamin related protein1; Dynamins - genetics; Gene Expression Regulation; GTP Phosphohydrolases - genetics; Humans; Lipid Metabolism - genetics; Lipids - genetics; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial dynamics; Mitochondrial Dynamics - genetics; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Proteins - genetics; Mitofusin1; Mitofusin2; Phosphatidylcholine; Phosphatidylcholines - metabolism; Reactive Oxygen Species - metabolism; StarD7
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2021.159029

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. •Different StarD7 expression levels impact on mitochondrial morphology.•StarD7.I increased expression, but not StarD7.II, induces mitochondrial fragmentation.•StarD7 silencing leads to mitochondrial fragmentation with a donut phenotype.•StarD7 levels modulate the expression of mitochondrial fusion/fission key proteins.•Mitochondrial morphology in StarD7.I overexpressed cells is dependent on Drp1 activity.