StarD7 deficiency switches on glycolysis and promotes mitophagy flux in C2C12 myoblasts

ROJAS, MARÍA L.; MUÑOZ, JUAN P.; FLORES-MARTÍN, JÉSICA B.; SANCHEZ-FERNANDEZ-DE-LANDA, PAULA; CRUZ DEL PUERTO, MARIANO; GENTI-RAIMONDI, SUSANA; ZORZANO, ANTONIO

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2023

1742-464X

StarD7 is a member of the START protein family required for phosphati-dylcholine delivery to the mitochondria, thus key to maintain mitochon-drial structure. Its deficiency has been associated with an impairment ofcellular processes, such as proliferation and migration, and it has also beenreported that it is needed in myogenic differentiation. Here, we show thatStarD7 deficiency in C2C12 muscle cells results in the accumulation ofabnormal mitochondria, a reduced number of mitochondria per cell areaand increased glycolysis. In addition, StarD7-deficient cells undergo anincrease in mitochondria-ER contact sites, reduced connexin 43 expression,and disturbances in lipid handling, evidenced by lipid droplet accumulationand decreased levels in phosphatidylserine synthase 1 and 2 expression.Interestingly, StarD7-deficient cells showed alterations in mitophagymarkers. We observed accumulation of LC3B-II and BNIP3 proteins inmitochondria-enriched fractions and accumulation of autophagolysosomaland lysosomal vesicles in StarD7-deficient cells. Furthermore, live-cellimaging experiments of StarD7 knockdown cells expressing mitochondria-targeted mKeima indicated an enhanced mitochondria delivery into lyso-somes. Importantly, StarD7 reconstitution in StarD7-deficient cells restoresLC3B-II expression in mitochondria-enriched fractions at similar levels to those observed in control cells. Collectively, these findings suggest thatStarD7-deficient C2C12 myoblasts are associated with altered cristae struc-ture, disturbances in neutral lipid accumulation, glucose metabolism, andincreased mitophagy flux. The alterations mentioned above allow for themaintenance of mitochondrial function.